The DOI matches its Crossref record; 275 of the 278 references it cites were found in a registry or an index; none of the 250 sources its claims cite is checked for support yet.
AMPK, Mitochondrial Function, and Cardiovascular Disease
Open accessAbstract
Adenosine monophosphate-activated protein kinase (AMPK) is in charge of numerous catabolic and anabolic signaling pathways to sustain appropriate intracellular adenosine triphosphate levels in response to energetic and/or cellular stress. In addition to its conventional roles as an intracellular energy switch or fuel gauge, emerging research has shown that AMPK is also a redox sensor and modulator, playing pivotal roles in maintaining cardiovascular processes and inhibiting disease progression. Pharmacological reagents, including statins, metformin, berberine, polyphenol, and resveratrol, all of which are widely used therapeutics for cardiovascular disorders, appear to deliver their protective/therapeutic effects partially via AMPK signaling modulation. The functions of AMPK during health and disease are far from clear. Accumulating studies have demonstrated crosstalk between AMPK and mitochondria, such as AMPK regulation of mitochondrial homeostasis and mitochondrial dysfunction causing abnormal AMPK activity. In this review, we begin with the description of AMPK structure and regulation, and then focus on the recent advances toward understanding how mitochondrial dysfunction controls AMPK and how AMPK, as a central mediator of the cellular response to energetic stress, maintains mitochondrial homeostasis. Finally, we systemically review how dysfunctional AMPK contributes to the initiation and progression of cardiovascular diseases via the impact on mitochondrial function.
Overview
AI snapshot
Written from the paper’s full text.
TL;DR
This review argues that AMPK is both a redox sensor/modulator and a central regulator of mitochondrial homeostasis, with bidirectional crosstalk: mitochondrial dysfunction can alter AMPK activity, while AMPK controls mitochondrial biogenesis, dynamics, mitophagy, and Ca²⁺ handling. Dysregulated AMPK–mitochondria signaling contributes to cardiovascular disease, and drugs such as metformin, berberine, statins, polyphenols, and resveratrol may act partly through AMPK.
Key findings
- AMPK is a heterotrimeric complex of α, β, and γ subunits; all isoform combinations produce 12 different AMPK complexes. It is activated by AMP/ADP and inhibited by ATP, with LKB1 and CAMKK2 as major upstream kinases; Thr172 phosphorylation increases AMPK activity about 100-fold, while allosteric regulation changes activity up to tenfold in mammalian cells and about twofold in recombinant bacterially produced AMPK.
- AMPK functions as a redox sensor and antioxidant modulator: ROS/RNS can activate AMPK via energy stress and/or LKB1–CaMKK signaling, while activated AMPK suppresses mitochondrial and NOX-derived ROS and upregulates antioxidant genes including CAT, SOD1, SOD2, and UCP2, often through PGC1α.
- AMPK regulates mitochondrial homeostasis by promoting mitochondrial biogenesis via PGC1α, controlling mitochondrial dynamics through MFF phosphorylation at Ser155/Ser173 and DRP1, regulating mitophagy through ULK1 and PINK1–PARKIN signaling, and modulating mitochondrial Ca²⁺ influx through MCU.
- In cardiovascular disease, AMPK is generally protective across atherosclerosis, ischemia, ischemia/reperfusion injury, vascular calcification, neointimal hyperplasia, cardiac hypertrophy, diabetes, inflammation, and obesity; the review notes that reperfusion failure occurs in approximately 30% of patients with acute myocardial infarction and that ischemic heart disease accounted for 15.96% of total global deaths in 2017.
Methods
- Not stated in the paper; the text is a narrative review that synthesizes cited literature rather than presenting original experimental data.
- The review covers AMPK structure and regulation, redox regulation of AMPK, mitochondrial control of AMPK, AMPK regulation of mitochondrial homeostasis, and AMPK–mitochondria signaling in cardiovascular and cardio-metabolic diseases.
- Main analysis is qualitative synthesis of mechanistic studies across cell, animal, and some human contexts; no systematic search strategy, inclusion criteria, or meta-analysis is described.
Limitations
- Stated: the authors note that the functions of AMPK during health and disease are “far from clear” and that the interplay within the AMPK–mitochondrial axis during cardiovascular disease initiation and progression is poorly investigated.
- Stated: limited evidence has focused on mitochondrial dynamics, mitochondrial biogenesis, and mitophagy, and the structural and functional changes to mitochondria under disease conditions remain “far beyond our current knowledge.”
- Evident from the text: as a narrative review, it does not provide primary data, systematic evidence grading, or quantitative synthesis; many mechanistic conclusions are drawn from preclinical cell and animal models, with clinical evidence cited more selectively.
Model-written summary. Check it against the paper before relying on it.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
180 Not checked yet · 9 Own interpretation · 5 No basis given
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Pharmacological reagents, including statins, metformin, berberine, polyphenol, and resveratrol, all of which are widely used therapeutics for cardiovascular disorders, appear to deliver their protective/therapeutic effects partially via AMPK signaling modulation.”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > Abstract
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: unclear — It is unclear why the paper says it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“Binding of AMP, and to a lesser degree ADP, to the γ-subunit stimulates AMPK activity via three mechanisms [27,28,29].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 2. AMPK Structure and Regulation > 2.2. Regulation of AMPK
What the sources say
- Not checked yetcites [27] Hardie, 2011, AMP-activated protein kinase: Also regulated by ADP?, Trends Biochem. Sci. source
- Not checked yetcites [28] Gowans, 2013, AMP is a true physiological regulator of AMP-activated protein kinase by both allosteric activation and enhancing net phosphorylation, Cell Metab. source
- Not checked yetcites [29] Ross, 2016, Differential regulation by AMP and ADP of AMPK complexes containing different gamma subunit isoforms, Biochem. J. source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“Second, AMP protects Thr172 against dephosphorylation by phosphatases [28,35,36,37].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 2. AMPK Structure and Regulation > 2.2. Regulation of AMPK
What the sources say
- Not checked yetcites [28] Gowans, 2013, AMP is a true physiological regulator of AMP-activated protein kinase by both allosteric activation and enhancing net phosphorylation, Cell Metab. source
- Not checked yetcites [35] Xiao, 2011, Structure of mammalian AMPK and its regulation by ADP, Nature source
- Not checked yetcites [36] Neumann, 2010, The PP1-R6 protein phosphatase holoenzyme is involved in the glucose-induced dephosphorylation and inactivation of AMP-activated protein kinase, a key regulator of insulin secretion, in MIN6 beta cells, FASEB J.
- Not checked yetcites [37] Joseph, 2015, Inhibition of AMP kinase by the protein phosphatase 2a heterotrimer, PP2APpp2r2d, J. Biol. Chem. source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“Once activated, AMPK redirects metabolism toward increased catabolism or decreased anabolism through the phosphorylation of key proteins across multiple pathways, including protein synthesis (e.g., mammalian target of rapamycin complex (1) [2,3], lipid homeostasis (e.g., acetyl coenzyme A carboxylase, ACC) [4,5], glucose metabolism (e.g., phosphofructokinase (2) [6], and mitochondrial homeostasis”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 1. Introduction
What the sources say
- Not checked yetcites [2] Gwinn, 2008, AMPK phosphorylation of raptor mediates a metabolic checkpoint, Mol. Cell source
- Not checked yetcites [3] Inoki, 2003, TSC2 mediates cellular energy response to control cell growth and survival, Cell source
- Not checked yetcites [4] Carling, 1987, A common bicyclic protein kinase cascade inactivates the regulatory enzymes of fatty acid and cholesterol biosynthesis, FEBS Lett. source
- Not checked yetcites [5] Munday, 1988, Identification by amino acid sequencing of three major regulatory phosphorylation sites on rat acetyl-CoA carboxylase, Eur. J. Biochem. source
- Not checked yetcites [7] Jager, 2007, AMP-activated protein kinase (AMPK) action in skeletal muscle via direct phosphorylation of PGC-1alpha, Proc. Natl. Acad. Sci. USA source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“AMPK is activated by energy stress and/or cellular stress in response to increased ATP consumption (e.g., exercise, cell proliferation, and anabolism) or decreased ATP production (e.g., low glucose levels, oxidative stress, and hypoxia), which are sensed as low ratios of ATP-to-AMP/ADP.”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 2. AMPK Structure and Regulation > 2.2. Regulation of AMPK
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Overall, activated AMPK balances energy levels by raising ATP synthesis and/or reducing ATP consumption.”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 1. Introduction
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Third, AMP causes the allosteric activation of AMPK that has already been phosphorylated on Thr172.”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 2. AMPK Structure and Regulation > 2.2. Regulation of AMPK
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“Under conditions of insufficient energy, AMPK activates upon its binding with AMP or adenosine diphosphate (ADP) [1].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 1. Introduction
What the sources say
- Not checked yetcites [1] Hardie, 2012, AMPK: A nutrient and energy sensor that maintains energy homeostasis, Nat. Rev. Mol. Cell Biol. source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“For instance, exposure of exogenous hydrogen peroxide to C2C12 cells led to a dose-dependent increase in AMPK activity by decreasing the ATP-to-ADP ratio [44].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 2. AMPK Structure and Regulation > 2.2. Regulation of AMPK
What the sources say
- Not checked yetcites [44] Hinchy, 2018, Mitochondria-derived ROS activate AMP-activated protein kinase (AMPK) indirectly, J. Biol. Chem. source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“The protective effects of fucoxanthin were attributed to activation of the AMPK-protein kinase C-NOX signaling pathway.”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 5. AMPK, Mitochondrial Function, and CVDs > 5.1. Atherosclerosis
What the sources say
- Not checked yetcites [129] Ou, 2019, Fucoxanthin protects against oxLDL-induced endothelial damage via activating the AMPK-Akt-CREB-PGC1alpha pathway, Mol. Nutr. Food Res. source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- It may state two separate claims as one. 71
- Probably not a substantial claim. 21
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In addition to its conventional roles as an intracellular energy switch or fuel gauge, emerging research has shown that AMPK is also a redox sensor and modulator, playing pivotal roles in maintaining cardiovascular processes and inhibiting disease progression.”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > Abstract
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“In humans, each subunit has multiple distinct isoforms encoded by different genes: the α-subunit has two isoforms, α1 and α2, encoded by gene PRKAA1 and PRKAA2, respectively [20]; the β-subunit has two isoforms, β1 and β2, encoded by gene PRKAB1 and PRKAB2, respectively [21]; and the γ-subunit has three isoforms, γ1, γ2, and γ3, encoded by gene PRKAG1, PRKAG2, and PRKAG3, respectively [22].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 2. AMPK Structure and Regulation > 2.1. AMPK Structure
What the sources say
- Not checked yetcites [20] Stapleton, 1996, Mammalian AMP-activated protein kinase subfamily, J. Biol. Chem. source
- Not checked yetcites [21] Thornton, 1998, Identification of a novel AMP-activated protein kinase beta subunit isoform that is highly expressed in skeletal muscle, J. Biol. Chem. source
- Not checked yetcites [22] Cheung, 2000, Characterization of AMP-activated protein kinase gamma-subunit isoforms and their role in AMP binding, Biochem. J. source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Activation loop phosphorylation increases AMPK activity by about 100-fold, while allosteric regulation changes AMPK activity up to tenfold in mammalian cells and about twofold in recombinant, bacterially produced AMPK [26,28,38,39].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 2. AMPK Structure and Regulation > 2.2. Regulation of AMPK
What the sources say
- Not checked yetcites [26] Xiao, 2007, Structural basis for AMP binding to mammalian AMP-activated protein kinase, Nature source
- Not checked yetcites [28] Gowans, 2013, AMP is a true physiological regulator of AMP-activated protein kinase by both allosteric activation and enhancing net phosphorylation, Cell Metab. source
- Not checked yetcites [38] Sanders, 2007, Defining the mechanism of activation of AMP-activated protein kinase by the small molecule A-769662, a member of the thienopyridone family, J. Biol. Chem. source
- Not checked yetcites [39] Davies, 1995, 5’-AMP inhibits dephosphorylation, as well as promoting phosphorylation, of the AMP-activated protein kinase. Studies using bacterially expressed human protein phosphatase-2C alpha and native bovine protein phosphatase-2AC, FEBS Lett. source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“ROS are plenty of free radicals and chemically reactive molecules derived from oxygen molecule [41].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 2. AMPK Structure and Regulation > 2.2. Regulation of AMPK
What the sources say
- Not checked yetcites [41] Alfadda, 2012, Reactive oxygen species in health and disease, J. Biomed. Biotechnol. source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Accumulating studies have demonstrated crosstalk between AMPK and mitochondria, such as AMPK regulation of mitochondrial homeostasis and mitochondrial dysfunction causing abnormal AMPK activity.”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > Abstract
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: unclear — It is unclear why the paper says it holds.
It may state two separate claims as one.
In the paper
“Each AMPK complex is comprised of an α-subunit, a β-subunit, and a γ-subunit, and all possible combinations produce 12 different AMPK complexes [23].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 2. AMPK Structure and Regulation > 2.1. AMPK Structure
What the sources say
- Not checked yetcites [23] Ross, 2016, AMP-activated protein kinase: A cellular energy sensor that comes in 12 flavours, FEBS J. source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“The γ-subunit allows AMPK to react to changes in the level of AMP, ADP, and ATP, as it includes four tandem cystathionine β synthase motifs that allow AMPK to bind adenine nucleotides [26].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 2. AMPK Structure and Regulation > 2.1. AMPK Structure
What the sources say
- Not checked yetcites [26] Xiao, 2007, Structural basis for AMP binding to mammalian AMP-activated protein kinase, Nature source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“Excessive production of ROS, usually termed oxidative stress, are caused by increased production and/or insufficient presence of endogenous antioxidants [41].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 2. AMPK Structure and Regulation > 2.2. Regulation of AMPK
What the sources say
- Not checked yetcites [41] Alfadda, 2012, Reactive oxygen species in health and disease, J. Biomed. Biotechnol. source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“Most ROS are generated as byproducts of mitochondrial electron transportation from the reduction of molecular oxygen to produce superoxide [41].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 2. AMPK Structure and Regulation > 2.2. Regulation of AMPK
What the sources say
- Not checked yetcites [41] Alfadda, 2012, Reactive oxygen species in health and disease, J. Biomed. Biotechnol. source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“Oxidative stress is considered detrimental because of its damage to fats, deoxyribonucleic acid, and proteins in a cell, which can lead to numerous diseases such as diabetes, cancer, neurodegenerative disease, and cardiovascular disease (CVD) [41].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 2. AMPK Structure and Regulation > 2.2. Regulation of AMPK
What the sources say
- Not checked yetcites [41] Alfadda, 2012, Reactive oxygen species in health and disease, J. Biomed. Biotechnol. source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
In the paper
“AMPK, a heterotrimeric complex, is composed of a catalytic α-subunit and beta (β) and gamma (γ) regulatory subunits [19].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 2. AMPK Structure and Regulation > 2.1. AMPK Structure
What the sources say
- Not checked yetcites [19] Yan, Y., Zhou, X.E., Xu, H.E., and Melcher, K. (2018). Structure and physiological regulation of AMPK. Int. J. Mol. Sci., 19. source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“The β-subunit includes a carbohydrate-binding module that grants AMPK to bind to glycogen [25].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 2. AMPK Structure and Regulation > 2.1. AMPK Structure
What the sources say
- Not checked yetcites [25] Hudson, 2003, A novel domain in AMP-activated protein kinase causes glycogen storage bodies similar to those seen in hereditary cardiac arrhythmias, Curr. Biol. source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“Lastly, allosteric AMPK activation can also occur in non-phosphorylated AMPK, with even higher fold activation than phosphorylated AMPK [40].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 2. AMPK Structure and Regulation > 2.2. Regulation of AMPK
What the sources say
- Not checked yetcites [40] Willows, 2017, Phosphorylation of AMPK by upstream kinases is required for activity in mammalian cells, Biochem. J. source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
In the paper
“The α-subunit is essential, and a double knockout (KO) of AMPKα1 and AMPKα2 in mice gives rise to embryonic lethality [24].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 2. AMPK Structure and Regulation > 2.1. AMPK Structure
What the sources say
- Not checked yetcites [24] Viollet, 2009, AMPK: Lessons from transgenic and knockout animals, Front. Biosci. (Landmark Ed.) source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“The α-subunit contains the kinase domain and a critical residue (Thr174 in α1-subunit and Thr172 in α2-subunit, hereafter referred to as Thr172) that is phosphorylated by upstream kinases [1].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 2. AMPK Structure and Regulation > 2.1. AMPK Structure
What the sources say
- Not checked yetcites [1] Hardie, 2012, AMPK: A nutrient and energy sensor that maintains energy homeostasis, Nat. Rev. Mol. Cell Biol. source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Liver kinase B 1 (LKB1) [32] and calcium/calmodulin-dependent protein kinase kinase (CAMKK) 2 [33,34] can be employed as the two main mammalian upstream molecules that phosphorylate AMPK.”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 2. AMPK Structure and Regulation > 2.2. Regulation of AMPK
What the sources say
- Not checked yetcites [32] Woods, 2003, LKB1 is the upstream kinase in the AMP-activated protein kinase cascade, Curr. Biol. source
- Not checked yetcites [33] Fujiwara, 2016, Differential AMP-activated Protein Kinase (AMPK) Recognition mechanism of Ca2+/calmodulin-dependent protein kinase kinase isoforms, J. Biol. Chem. source
- Not checked yetcites [34] Hawley, 2005, Calmodulin-dependent protein kinase kinase-beta is an alternative upstream kinase for AMP-activated protein kinase, Cell Metab. source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“In H4IIEC3 cells, exogenous hydrogen peroxide transiently increased the level of phosphor-AMPK by LKB1 signaling, while exogenous hydrogen peroxide promoted AMPK phosphorylation in HeLa cells by CaMKK signaling [42].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 2. AMPK Structure and Regulation > 2.2. Regulation of AMPK
What the sources say
- Not checked yetcites [42] Liangpunsakul, 2008, Effect of ethanol on hydrogen peroxide-induced AMPK phosphorylation, Am. J. Physiol. Gastrointest. Liver Physiol. source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“TPr agonists-activated AMPK was mediated by hydrogen peroxide, as demonstrated by the results showing overexpression of catalase (CAT) abolished Tpr agonists-induced AMPK activation [61].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 2. AMPK Structure and Regulation > 2.2. Regulation of AMPK
What the sources say
- Not checked yetcites [61] Zhang, 2008, Thromboxane receptor activates the AMP-activated protein kinase in vascular smooth muscle cells via hydrogen peroxide, Circ. Res. source
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Exogenous or glucose oxidase-generated hydrogen peroxide induced direct S-glutathionylation on the AMPKα subunit at Cys299 and Cys304, which contributes to AMPK activation [48].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 2. AMPK Structure and Regulation > 2.2. Regulation of AMPK
What the sources say
- Not checked yetcites [48] Zmijewski, 2010, Exposure to hydrogen peroxide induces oxidation and activation of AMP-activated protein kinase, J. Biol. Chem. source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“Its decrease occurs in response to lipid infiltration, oxidative stress, and inflammatory factors, which play a vital role in endothelial dysfunction [153].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 5. AMPK, Mitochondrial Function, and CVDs > 5.1. Atherosclerosis
What the sources say
- Not checked yetcites [153] Chen, 2018, Nitric oxide bioavailability dysfunction involves in atherosclerosis, Biomed. Pharmacother. source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Additional evidence supporting AMPK protection against oxidative stress is that AMPK negatively regulates NOX by reducing its phosphorylation and preventing P47phox’s translocation to membrane [70,151].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 5. AMPK, Mitochondrial Function, and CVDs > 5.1. Atherosclerosis
What the sources say
- Not checked yetcites [70] Wang, 2010, AMPKalpha2 deletion causes aberrant expression and activation of NAD(P)H oxidase and consequent endothelial dysfunction in vivo: Role of 26S proteasomes, Circ. Res. source
- Not checked yetcites [151] McCarty, 2009, AMP-activated kinase may suppress NADPH oxidase activation in vascular tissues, Med. Hypotheses source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Moreover, the suppression of oxidative stress, in turn, blunted the activation of the protein kinase B-cyclic AMP-responsive element binding protein–PGC1α pathway, which ameliorated mitochondrial dysfunction and apoptosis [129].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 5. AMPK, Mitochondrial Function, and CVDs > 5.1. Atherosclerosis
What the sources say
- Not checked yetcites [129] Ou, 2019, Fucoxanthin protects against oxLDL-induced endothelial damage via activating the AMPK-Akt-CREB-PGC1alpha pathway, Mol. Nutr. Food Res. source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Alternatively, some studies showed that ROS directly activated AMPK independent of changes in ADP, AMP, and ATP.”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 2. AMPK Structure and Regulation > 2.2. Regulation of AMPK
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“AMPK suppresses protein kinase C activity and prevents protein kinase C modulation of p47phox phosphorylation [152].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 5. AMPK, Mitochondrial Function, and CVDs > 5.1. Atherosclerosis
What the sources say
- Not checked yetcites [152] Ou, 2013, Ginkgo biloba extract attenuates oxLDL-induced endothelial dysfunction via an AMPK-dependent mechanism, J. Appl. Physiol. (1985) source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“It is well established that the ROS-induced energy stress strongly activates AMPK, which is likely the main mechanism of ROS-mediated AMPK activation.”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 2. AMPK Structure and Regulation > 2.2. Regulation of AMPK
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Similarly, in NIH-3T3 cells, exogenous hydrogen peroxide transiently activated AMPK in a dose-dependent manner, which was associated with an increased AMP-to-ATP ratio [45].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 2. AMPK Structure and Regulation > 2.2. Regulation of AMPK
What the sources say
- Not checked yetcites [45] Choi, 2001, The regulation of AMP-activated protein kinase by H(2)O(2), Biochem. Biophys. Res. Commun. source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Vasculature I/R injury alleviates the efficiency of reperfusion therapy and compromises the clinical benefits of patients with acute MI [181].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 5. AMPK, Mitochondrial Function, and CVDs > 5.3. I/R
What the sources say
- Not checked yetcites [181] Ndrepepa, 2010, 5-year prognostic value of no-reflow phenomenon after percutaneous coronary intervention in patients with acute myocardial infarction, J. Am. Coll. Cardiol. source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“However, with increasing mitochondria, the level of ROS is also increased as mitochondrial byproducts, which can result in oxidative damage of mitochondria [176].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 5. AMPK, Mitochondrial Function, and CVDs > 5.2. Ischemia
What the sources say
- Not checked yetcites [176] Fischer, 2012, Mitochondrial quality control: An integrated network of pathways, Trends Biochem. Sci. source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Mitochondria-targeted esculetin, capable of scavenging mitochondrial ROS, greatly alleviated angiotensin II-induced monocyte infiltration, atherosclerotic plaque formation, and serum pro-inflammatory cytokine production in apolipoprotein E KO mice [131].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 5. AMPK, Mitochondrial Function, and CVDs > 5.1. Atherosclerosis
What the sources say
- Not checked yetcites [131] Karnewar, 2016, Mitochondria-targeted esculetin alleviates mitochondrial dysfunction by AMPK-mediated nitric oxide and SIRT3 regulation in endothelial cells: Potential implications in atherosclerosis, Sci. Rep. source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“During early reperfusion, treatment with metformin augmented I/R-induced AMPK activation and significantly increased eNOS phosphorylation at ser1177 [183].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 5. AMPK, Mitochondrial Function, and CVDs > 5.3. I/R
What the sources say
- Not checked yetcites [183] Calvert, 2008, Acute metformin therapy confers cardioprotection against myocardial infarction via AMPK-eNOS-mediated signaling, Diabetes source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“The apoptosis induces endothelial swelling, microvascular spasms, and capillary obstruction, which slows or even stops microcirculation blood flow following reperfusion [179].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 5. AMPK, Mitochondrial Function, and CVDs > 5.3. I/R
What the sources say
- Not checked yetcites [179] Kloner, 1974, The “no-reflow” phenomenon after temporary coronary occlusion in the dog, J. Clin. Investig. source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“These results suggest that AMPK participates in mitophagy regulation, which thereby provides a valuable therapeutic target for ischemic heart diseases.”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 5. AMPK, Mitochondrial Function, and CVDs > 5.2. Ischemia
What the sources say
- Not checked yetcites [133] Zhang, 2018, AMPK activation serves a critical role in mitochondria quality control via modulating mitophagy in the heart under chronic hypoxia, Int. J. Mol. Med.
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Similarly, in comparison with the WT cells, tube formation in mouse arterial endothelial cells isolated from either AMPKα1−/− or AMPKα2−/− mice was significantly impaired, exhibiting oxidative stress and reduced expression of UCP2.”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 5. AMPK, Mitochondrial Function, and CVDs > 5.2. Ischemia
What the sources say
- Not checked yetcites [132] Xu, 2011, Impaired expression of uncoupling protein 2 causes defective postischemic angiogenesis in mice deficient in AMP-activated protein kinase alpha subunits, Arterioscler. Thromb. Vasc. Biol. source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Mitophagy increased significantly in cardiomyocytes exposed to hypoxic conditions, which was accompanied by AMPK activation [133].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 5. AMPK, Mitochondrial Function, and CVDs > 5.2. Ischemia
What the sources say
- Not checked yetcites [133] Zhang, 2018, AMPK activation serves a critical role in mitochondria quality control via modulating mitophagy in the heart under chronic hypoxia, Int. J. Mol. Med.
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Under chronic hypoxia, PGC1α is upregulated, resulting in a subsequent increase of mitochondrial biogenesis [175].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 5. AMPK, Mitochondrial Function, and CVDs > 5.2. Ischemia
What the sources say
- Not checked yetcites [175] Zhu, 2010, Hypoxia induces PGC-1alpha expression and mitochondrial biogenesis in the myocardium of TOF patients, Cell Res. source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Treatment of cardiomyocytes with carvedilol augmented phosphorylation of AMPK and its downstream substrate ACC, and ameliorated hypoxia-induced impairment [182].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 5. AMPK, Mitochondrial Function, and CVDs > 5.3. I/R
What the sources say
- Not checked yetcites [182] Hu, 2019, The cardioprotective effects of carvedilol on ischemia and reperfusion injury by AMPK signaling pathway, Biomed. Pharmacother. source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Mechanically, AMPK increased glucose uptake and glucose transporter 4 translocation [171], decreased apoptosis, improved post-ischemic recovery, and limited myocardial infarction (MI) [172,173].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 5. AMPK, Mitochondrial Function, and CVDs > 5.2. Ischemia
What the sources say
- Not checked yetcites [172] Ma, 2010, Impaired macrophage migration inhibitory factor-AMP-activated protein kinase activation and ischemic recovery in the senescent heart, Circulation source
- Not checked yetcites [173] Russell, 2004, AMP-activated protein kinase mediates ischemic glucose uptake and prevents postischemic cardiac dysfunction, apoptosis, and injury, J. Clin. Investig. source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Consistently, when AMPK activation was blocked, mitophagy decreased as well, which subsequently gave rise to cardiomyocyte apoptosis [133].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 5. AMPK, Mitochondrial Function, and CVDs > 5.2. Ischemia
What the sources say
- Not checked yetcites [133] Zhang, 2018, AMPK activation serves a critical role in mitochondria quality control via modulating mitophagy in the heart under chronic hypoxia, Int. J. Mol. Med.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“I/R injury causes myocardial damage and increases 30-day mortality rates [180].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 5. AMPK, Mitochondrial Function, and CVDs > 5.3. I/R
What the sources say
- Not checked yetcites [180] Abbate, 2008, No-reflow: The next challenge in treatment of ST-elevation acute myocardial infarction, Eur. Heart J. source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Mechanically, AMPK increased glucose uptake and glucose transporter 4 translocation [171], decreased apoptosis, improved post-ischemic recovery, and limited myocardial infarction (MI) [172,173].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 5. AMPK, Mitochondrial Function, and CVDs > 5.2. Ischemia
What the sources say
- Not checked yetcites [171] Miller, 2008, Macrophage migration inhibitory factor stimulates AMP-activated protein kinase in the ischaemic heart, Nature source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“In vitro mechanism studies showed that I/R triggered a DRP1-dependent mitochondrial fragmentation, which subsequently led to oligomerization of voltage-dependent anion channel 1, liberation of hexokinase 2, opening of mitochondrial permeability transition pore, upregulation of PINK1–PARKIN signaling, and eventual mitophagy-mediated cell death [134].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 5. AMPK, Mitochondrial Function, and CVDs > 5.3. I/R
What the sources say
- Not checked yetcites [134] Zhou, 2017, Melatonin protects cardiac microvasculature against ischemia/reperfusion injury via suppression of mitochondrial fission-VDAC1-HK2-mPTP-mitophagy axis, J. Pineal. Res. source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“The mitochondrial open reading frame of the 12S rRNA-c (MOTS-c) is a bioactive mitochondrial-derived peptide shown to activate the AMPK pathway and modulate metabolic homeostasis [193].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 5. AMPK, Mitochondrial Function, and CVDs > 5.4. Vascular Calcification (VC)
What the sources say
- Not checked yetcites [193] Lee, 2015, The mitochondrial-derived peptide MOTS-c promotes metabolic homeostasis and reduces obesity and insulin resistance, Cell Metab. source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Further mechanism studies showed that nitrite activated protein kinase A, which in turn suppressed DRP1-dependent mitochondrial fission, augmented ΔΨm, and promoted superoxide production [135].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 5. AMPK, Mitochondrial Function, and CVDs > 5.3. I/R
What the sources say
- Not checked yetcites [135] Mo, 2014, Nitrite activates protein kinase A in normoxia to mediate mitochondrial fusion and tolerance to ischaemia/reperfusion, Cardiovasc. Res. source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Melatonin promoted cell survival via AMPKα activation, accompanied by phosphor-DRP1-S616 reduction and phosphor-DRP1-S637 elevation, which normalized mitochondrial fission [134].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 5. AMPK, Mitochondrial Function, and CVDs > 5.3. I/R
What the sources say
- Not checked yetcites [134] Zhou, 2017, Melatonin protects cardiac microvasculature against ischemia/reperfusion injury via suppression of mitochondrial fission-VDAC1-HK2-mPTP-mitophagy axis, J. Pineal. Res. source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Melatonin significantly decreased myocadiac infarction, improved cardiac function, normalized blood flow, and lowered microcirculation perfusion impairment [134].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 5. AMPK, Mitochondrial Function, and CVDs > 5.3. I/R
What the sources say
- Not checked yetcites [134] Zhou, 2017, Melatonin protects cardiac microvasculature against ischemia/reperfusion injury via suppression of mitochondrial fission-VDAC1-HK2-mPTP-mitophagy axis, J. Pineal. Res. source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Histological analysis revealed that administration of melatonin restored the endothelial barrier, promoted eNOS expression, decreased inflammatory cell infiltration, and lowered endothelial damage in cardiac microcirculation endothelial cells [134].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 5. AMPK, Mitochondrial Function, and CVDs > 5.3. I/R
What the sources say
- Not checked yetcites [134] Zhou, 2017, Melatonin protects cardiac microvasculature against ischemia/reperfusion injury via suppression of mitochondrial fission-VDAC1-HK2-mPTP-mitophagy axis, J. Pineal. Res. source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“In parallel, phosphorylated AMPK increased and the expression of endothelin B (ETB) and angiotensin II receptor type 1 (AT1) receptors decreased after MOTS-c treatment [136].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 5. AMPK, Mitochondrial Function, and CVDs > 5.4. Vascular Calcification (VC)
What the sources say
- Not checked yetcites [136] Wei, 2020, Mitochondrial-derived peptide MOTS-c attenuates vascular calcification and secondary myocardial remodeling via adenosine monophosphate-activated protein kinase signaling pathway, Cardiorenal. Med. source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“These results indicate that TSPO regulates neointimal formation after vascular injury via stimulating VSMC proliferation and migration, which is likely dependent on AMPK suppression [137].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 5. AMPK, Mitochondrial Function, and CVDs > 5.5. Neointimal Hyperplasia Formation
What the sources say
- Not checked yetcites [137] Wu, 2020, TSPO ligands prevent the proliferation of vascular smooth muscle cells and attenuate neointima formation through AMPK activation, Acta Pharmacol. Sin. source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Neointimal hyperplasia narrows the luminal diameter, leading to decreased blood flow and recurrence of anginal symptoms [196].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 5. AMPK, Mitochondrial Function, and CVDs > 5.5. Neointimal Hyperplasia Formation
What the sources say
- Not checked yetcites [196] Schwartz, 1997, Perspectives series: Cell adhesion in vascular biology. Smooth muscle migration in atherosclerosis and restenosis, J. Clin. Investig. source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“The prevention of mitochondrial fission further restored the interaction between voltage-dependent anion channel 1 and hexokinase 2, stopped mitochondrial permeability transition pore opening, and PINK1–PARKIN activation, ultimately blunting cell death [134].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 5. AMPK, Mitochondrial Function, and CVDs > 5.3. I/R
What the sources say
- Not checked yetcites [134] Zhou, 2017, Melatonin protects cardiac microvasculature against ischemia/reperfusion injury via suppression of mitochondrial fission-VDAC1-HK2-mPTP-mitophagy axis, J. Pineal. Res. source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“The loss of AMPK activity is believed to be pro-hypertrophic because lines of molecular signaling pathways that control cell growth are attenuated by AMPK activation [197,198,199].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 5. AMPK, Mitochondrial Function, and CVDs > 5.6. Cardiac Hypertrophy
What the sources say
- Not checked yetcites [197] Chan, 2008, Resveratrol inhibits cardiac hypertrophy via AMP-activated protein kinase and Akt, J. Biol. Chem. source
- Not checked yetcites [198] Chan, 2004, Activation of AMP-activated protein kinase inhibits protein synthesis associated with hypertrophy in the cardiac myocyte, J. Biol. Chem. source
- Not checked yetcites [199] Browne, 2004, Stimulation of the AMP-activated protein kinase leads to activation of eukaryotic elongation factor 2 kinase and to its phosphorylation at a novel site, serine 398, J. Biol. Chem. source
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Moreover, ROS scavenging blocks AMPK activation and blunts nitrite-induced cardioprotection after H/R [135].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 5. AMPK, Mitochondrial Function, and CVDs > 5.3. I/R
What the sources say
- Not checked yetcites [135] Mo, 2014, Nitrite activates protein kinase A in normoxia to mediate mitochondrial fusion and tolerance to ischaemia/reperfusion, Cardiovasc. Res. source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“In the meantime, DRP1-S616 phosphorylation was decreased, while DRP1-S637 phosphorylation was increased, ultimately leading to mitochondrial fission [229].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 6. Cardio-Metabolic Diseases > 6.1. Diabetes
What the sources say
- Not checked yetcites [229] Zhou, 2018, Empagliflozin rescues diabetic myocardial microvascular injury via AMPK-mediated inhibition of mitochondrial fission, Redox Biol. source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“However, some pharmacological AMPK activators, such as MK-8722 [203], cause cardiac hypertrophy, which is considered the main side effect of pharmacological pan-AMPK activation [17].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 5. AMPK, Mitochondrial Function, and CVDs > 5.6. Cardiac Hypertrophy
What the sources say
- Not checked yetcites [203] Feng, 2018, Discovery of MK-8722: A systemic, direct pan-activator of amp-activated protein kinase, ACS Med. Chem. Lett. source
- Not checked yetcites [17] Myers, 2017, Systemic pan-AMPK activator MK-8722 improves glucose homeostasis but induces cardiac hypertrophy, Science source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“In failing heart samples from patients or TAC mice, the isoform of AMPKα shifted from α2 to α1, which is associated with reduced mitophagy and dysfunctional mitochondria [117].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 5. AMPK, Mitochondrial Function, and CVDs > 5.6. Cardiac Hypertrophy
What the sources say
- Not checked yetcites [117] Wang, 2018, AMPKalpha2 protects against the development of heart failure by enhancing mitophagy via pink1 phosphorylation, Circ. Res. source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Clusterin, which exerts beneficial effects in ECs under diabetic conditions (both type 1 and type 2), inhibits mitochondrial fragmentation while activating AMPK [228].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 6. Cardio-Metabolic Diseases > 6.1. Diabetes
What the sources say
- Not checked yetcites [228] Ren, 2019, Clusterin ameliorates endothelial dysfunction in diabetes by suppressing mitochondrial fragmentation, Free Radic. Biol. Med. source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Consistently, SIRT5 ablation attenuated cardiac hypertrophy and cardiac dysfunction in the TAC model, which is accompanied by the reduction of ATP, increase of AMP-to-ATP ratio, and enhancement of AMPK activity [138].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 5. AMPK, Mitochondrial Function, and CVDs > 5.6. Cardiac Hypertrophy
What the sources say
- Not checked yetcites [138] Zhang, M., Wu, J., Sun, R., Tao, X., Wang, X., Kang, Q., Wang, H., Zhang, L., Liu, P., and Zhang, J. (2019). SIRT5 deficiency suppresses mitochondrial ATP production and promotes AMPK activation in response to energy stress. PLoS ONE, 14. source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Endothelial dysfunction is attributed to many causes, including oxidative stress, chronic inflammation, and endothelium activation, in diabetes, which exhibits excessive free fatty acid (FFA), insulin resistance, and/or hyperglycemia [216,217].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 6. Cardio-Metabolic Diseases > 6.1. Diabetes
What the sources say
- Not checked yetcites [216] Zhang, 2012, The link between metabolic abnormalities and endothelial dysfunction in type 2 diabetes: An update, Basic Res. Cardiol. source
- Not checked yetcites [217] Kim, 2006, Reciprocal relationships between insulin resistance and endothelial dysfunction: Molecular and pathophysiological mechanisms, Circulation source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“SIRT5 deficiency attenuated ATP production from mitochondrial ETC, increased the AMP-to-ATP ratio, and in turn activated AMPK in both cultured cells and hearts under the conditions of energy stress [138].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 5. AMPK, Mitochondrial Function, and CVDs > 5.6. Cardiac Hypertrophy
What the sources say
- Not checked yetcites [138] Zhang, M., Wu, J., Sun, R., Tao, X., Wang, X., Kang, Q., Wang, H., Zhang, L., Liu, P., and Zhang, J. (2019). SIRT5 deficiency suppresses mitochondrial ATP production and promotes AMPK activation in response to energy stress. PLoS ONE, 14. source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Both the conditions of hyperlipidemia and hyperglycemia impair mitochondrial dynamics by shifting the balance to excessive mitochondrial fission, leading to mitochondrial ROS over production and ETC impairment [221,222,223].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 6. Cardio-Metabolic Diseases > 6.1. Diabetes
What the sources say
- Not checked yetcites [221] LaRocca, 2014, Mitochondria-targeted antioxidant (MitoQ) ameliorates age-related arterial endothelial dysfunction in mice, J. Physiol. source
- Not checked yetcites [222] Huang, 2018, The uremic toxin hippurate promotes endothelial dysfunction via the activation of Drp1-mediated mitochondrial fission, Redox Biol. source
- Not checked yetcites [223] Yu, 2006, Increased production of reactive oxygen species in hyperglycemic conditions requires dynamic change of mitochondrial morphology, Proc. Natl. Acad. Sci. USA source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Thus, this study unveils a crucial role of SIRT5 in controlling cellular energy metabolism by AMPK activation upon energy stress, which further confirms the cardioprotective role of AMPK in left ventricular hypertrophy under the stress of pressure overload [138].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 5. AMPK, Mitochondrial Function, and CVDs > 5.6. Cardiac Hypertrophy
What the sources say
- Not checked yetcites [138] Zhang, M., Wu, J., Sun, R., Tao, X., Wang, X., Kang, Q., Wang, H., Zhang, L., Liu, P., and Zhang, J. (2019). SIRT5 deficiency suppresses mitochondrial ATP production and promotes AMPK activation in response to energy stress. PLoS ONE, 14. source
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“MAMs play a vital role in lipid transport, Ca2+ signaling, cell survival, and energy metabolism [234], and have been implicated in diseases including Alzheimer’s disease [235], cancer [236], lysosomal storage disease [237], diabetes mellitus [238,239], obesity, and metabolic disorders [240].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 6. Cardio-Metabolic Diseases > 6.1. Diabetes
What the sources say
- Not checked yetcites [234] Rowland, 2012, Endoplasmic reticulum-mitochondria contacts: Function of the junction, Nat. Rev. Mol. Cell Biol. source
- Not checked yetcites [235] Suski, 2017, Localization and processing of the amyloid-beta protein precursor in mitochondria-associated membranes, J. Alzheimers Dis.
- Not checked yetcites [236] Ando, 2018, Remodeling of Ca(2+) signaling in cancer: Regulation of inositol 1,4,5-trisphosphate receptors through oncogenes and tumor suppressors, Adv. Biol. Regul. source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
In the paper
“High glucose-driven inactivation of AMPK increased FUNDC1, resulting in aberrant MAM formation, mitochondrial Ca2+ increase, mitochondrial dysfunction, and cardiac dysfunction [139].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 6. Cardio-Metabolic Diseases > 6.1. Diabetes
What the sources say
- Not checked yetcites [139] Wu, 2019, Hyperglycemia-Driven Inhibition of AMP-activated protein kinase alpha2 induces diabetic cardiomyopathy by promoting mitochondria-associated endoplasmic reticulum membranes in vivo, Circulation source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Upregulation of XO was accompanied by excessive ROS production, resulting in the Ser616 phosphorylation as well as the mitochondrial migration of DRP1 [140].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 6. Cardio-Metabolic Diseases > 6.2. Inflammation
What the sources say
- Not checked yetcites [140] Cui, 2018, Melatonin alleviates inflammation-induced apoptosis in human umbilical vein endothelial cells via suppression of Ca(2+)-XO-ROS-Drp1-mitochondrial fission axis by activation of AMPK/SERCA2a pathway, Cell Stress Chaperones source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Vildagliptin improved mitochondrial dysfunction in diabetic ECs, possibly by blunting DRP1-dependent mitochondrial fission by inducing AMPK activation [230].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 6. Cardio-Metabolic Diseases > 6.1. Diabetes
What the sources say
- Not checked yetcites [230] Liu, 2019, Vildagliptin improves high glucose-induced endothelial mitochondrial dysfunction via inhibiting mitochondrial fission, J. Cell. Mol. Med. source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Thus, under diabetic conditions, ECs often have reduced eNOS activity and diminished NO production [259].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 6. Cardio-Metabolic Diseases > 6.3. Obesity
What the sources say
- Not checked yetcites [259] Dresner, 1999, Effects of free fatty acids on glucose transport and IRS-1-associated phosphatidylinositol 3-kinase activity, J. Clin. Investig. source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Importantly, melatonin activated AMPK, which was associated with the upregulation of sarcoplasmic/endoplasmic reticulum calcium ATPase 2a [140].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 6. Cardio-Metabolic Diseases > 6.2. Inflammation
What the sources say
- Not checked yetcites [140] Cui, 2018, Melatonin alleviates inflammation-induced apoptosis in human umbilical vein endothelial cells via suppression of Ca(2+)-XO-ROS-Drp1-mitochondrial fission axis by activation of AMPK/SERCA2a pathway, Cell Stress Chaperones source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Obesity-related type 2 diabetes patients often have elevated plasma FFAs, because of either increased amounts of FFAs released from large amounts of adipose tissue or impaired FFA clearance [258].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 6. Cardio-Metabolic Diseases > 6.3. Obesity
What the sources say
- Not checked yetcites [258] Boden, 2003, Effects of free fatty acids (FFA) on glucose metabolism: Significance for insulin resistance and type 2 diabetes, Exp. Clin. Endocrinol. Diabetes source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Further, melatonin-activated AMPK-sarcoplasmic/endoplasmic reticulum calcium ATPase 2a axis prevented calcium overload, XO-dependent ROS overproduction, DRP1-mediated mitochondrial fission, and apoptosis in lipopolysaccharide-treated cells [140].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 6. Cardio-Metabolic Diseases > 6.2. Inflammation
What the sources say
- Not checked yetcites [140] Cui, 2018, Melatonin alleviates inflammation-induced apoptosis in human umbilical vein endothelial cells via suppression of Ca(2+)-XO-ROS-Drp1-mitochondrial fission axis by activation of AMPK/SERCA2a pathway, Cell Stress Chaperones source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Lipopolysaccharide triggered cytosolic calcium overload, and in turn upregulated XO, whose activity is calcium-dependent [140].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 6. Cardio-Metabolic Diseases > 6.2. Inflammation
What the sources say
- Not checked yetcites [140] Cui, 2018, Melatonin alleviates inflammation-induced apoptosis in human umbilical vein endothelial cells via suppression of Ca(2+)-XO-ROS-Drp1-mitochondrial fission axis by activation of AMPK/SERCA2a pathway, Cell Stress Chaperones source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Study showed that mitochondrial outer membrane protein FUN14 domain containing 1 (FUNDC1) is essential for maintaining the MAM structure and ensuring appropriate Ca2+ transfer from the sarcoplasmic reticulum (i.e., ER in myocytes) to mitochondria in healthy hearts [241].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 6. Cardio-Metabolic Diseases > 6.1. Diabetes
What the sources say
- Not checked yetcites [241] Wu, 2017, Binding of FUN14 domain containing 1 with inositol 1,4,5-trisphosphate receptor in mitochondria-associated endoplasmic reticulum membranes maintains mitochondrial dynamics and function in hearts in vivo, Circulation source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“CRA activated AMPK in a LKB1-dependent manner, and AMPK silencing abrogated its inhibitory effect on DRP1 activation and mitochondrial fission [141].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 6. Cardio-Metabolic Diseases > 6.3. Obesity
What the sources say
- Not checked yetcites [141] Li, 2016, Inhibition of mitochondrial fission and NOX2 expression prevent nlrp3 inflammasome activation in the endothelium: The role of corosolic acid action in the amelioration of endothelial dysfunction, Antioxid. Redox Signal. source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“DRP1 knockdown attenuated PA-induced NOX2 activation, and knockdown of DRP1 or NOX2 suppressed PA-induced NACHT, LRR, and PYD domains-containing protein 3 inflammatory effect and, in the meantime, strengthened the inhibitory effects of CRA [141].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 6. Cardio-Metabolic Diseases > 6.3. Obesity
What the sources say
- Not checked yetcites [141] Li, 2016, Inhibition of mitochondrial fission and NOX2 expression prevent nlrp3 inflammasome activation in the endothelium: The role of corosolic acid action in the amelioration of endothelial dysfunction, Antioxid. Redox Signal. source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Obesity is closely associated with cardiac disorders, which is assumed to be a consequence of the adaption to an oversupply of high-fat substrates [262,263].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 6. Cardio-Metabolic Diseases > 6.3. Obesity
What the sources say
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“It is well-accepted that AMPK activation plays protective roles across diverse CVDs.”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 7. Perspectives
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper may give no reason why it holds.
In the paper
“These data collectively demonstrated that CRA prevented mitochondrial fission by regulating DRP1 phosphorylation at Ser637 in an AMPK-dependent manner, contributing to the blockage of NOX2-related oxidative stress and suppressing NACHT, LRR, and PYD domains-containing protein 3 inflammasome in the endothelium [141].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 6. Cardio-Metabolic Diseases > 6.3. Obesity
What the sources say
- Not checked yetcites [141] Li, 2016, Inhibition of mitochondrial fission and NOX2 expression prevent nlrp3 inflammasome activation in the endothelium: The role of corosolic acid action in the amelioration of endothelial dysfunction, Antioxid. Redox Signal. source
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Far beyond our current knowledge are the structural and functional changes to mitochondria that may be amplified under disease conditions.”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 7. Perspectives
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: fails — It may be too vague to check against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. It may be too vague to check against evidence. The paper’s conclusions may not depend on it. The paper may give no reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“AMPK has emerged as a guardian of mitochondria because almost all mitochondrial insults can activate AMPK.”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 7. Perspectives
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds. It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“However, the interplay within the AMPK–mitochondrial axis during the initiation and progression of CVDs is poorly investigated.”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 7. Perspectives
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper may give no reason why it holds.
In the paper
“Concomitantly, pomegranate extract activated AMPK, which may be responsible for the intervention of mitochondrial loss through promoting mitochondrial biogenesis and the attenuation of oxidative stress by means of upregulating phase II enzymes in HFD hearts [142].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 6. Cardio-Metabolic Diseases > 6.3. Obesity
What the sources say
- Not checked yetcites [142] Cao, 2015, Punicalagin, an active component in pomegranate, ameliorates cardiac mitochondrial impairment in obese rats via AMPK activation, Sci. Rep. source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“A direct functional connection between AMPK signaling and β-adrenergic responsiveness exists in the heart, and AMPK might be a valuable target to recover the decreased β-adrenergic responsive in the heart of obesity [270].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 6. Cardio-Metabolic Diseases > 6.3. Obesity
What the sources say
- Not checked yetcites [270] Bussey, 2018, Cardiac beta-adrenergic responsiveness of obese Zucker rats: The role of AMPK, Exp. Physiol. source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Limited evidence has focused on mitochondrial dynamics, mitochondrial biogenesis, and mitophagy, the three common functions of mitochondria that have been studied by cell biologists.”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 7. Perspectives
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper may give no reason why it holds.
In the paper
“Punicalagin, the major active component in pomegranate extract, protects against HFD-induced cardiac disorders by activating AMPK pathway and promoting mitochondrial biogenesis [142].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 6. Cardio-Metabolic Diseases > 6.3. Obesity
What the sources say
- Not checked yetcites [142] Cao, 2015, Punicalagin, an active component in pomegranate, ameliorates cardiac mitochondrial impairment in obese rats via AMPK activation, Sci. Rep. source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“The loss of AMPK activity exacerbated cardiac hypertrophy and dysfunctional contractility of HFD-fed mice [268].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 6. Cardio-Metabolic Diseases > 6.3. Obesity
What the sources say
- Not checked yetcites [268] Turdi, 2011, Deficiency in AMP-activated protein kinase exaggerates high fat diet-induced cardiac hypertrophy and contractile dysfunction, J. Mol. Cell. Cardiol. source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“C1q/tumor necrosis factor-related protein 9 exhibited anti-myocardial lipotoxicity effects and attenuated cardiac hypertrophy, likely via activation of the LKB1–AMPK signaling [269].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 6. Cardio-Metabolic Diseases > 6.3. Obesity
What the sources say
- Not checked yetcites [269] Zuo, 2020, CTRP9 knockout exaggerates lipotoxicity in cardiac myocytes and high-fat diet-induced cardiac hypertrophy through inhibiting the LKB1/AMPK pathway, J. Cell. Mol. Med. source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Increased body weight switches the substrate of the heart from fatty acid to sugar, resulting in fat accumulation around the heart and eventually inducing cardiac impairment and increasing the risk of MI [264,265].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 6. Cardio-Metabolic Diseases > 6.3. Obesity
What the sources say
- Not checked yetcites [264] Schram, 2008, Implications of myocardial matrix remodeling by adipokines in obesity-related heart failure, Trends Cardiovasc. Med. source
- Not checked yetcites [265] Look, 2009, Adipocyte fatty acid-binding protein suppresses cardiomyocyte contraction: A new link between obesity and heart disease, Circ. Res. source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper relies on this without support.
Mitochondria are the primary source of ATP production in the cell.
“Mitochondria are considered the primary source of ATP production in the cell.”
The paper relies on this without support.
Mitochondrial dysfunction occurs in the development of many cardiovascular diseases owing to production of ROS beyond control.
“Mitochondrial dysfunction occurs in the development of many CVDs such as atherosclerosis, ischemia-reperfusion (I/R) injury, hypertension, diabetes, cardiac hypertrophy, and heart failure (HF), owing to the production of ROS beyond control.”
The paper relies on this without support.
AMPK is widely expressed in the cardiovascular system.
“AMPK is widely expressed in the cardiovascular system.”
The paper relies on this without support.
The α1 isoform predominates in VSMCs, ECs, adipocytes, and monocytes/macrophages, whereas cardiomyocytes express much higher amounts of the α2 isoform.
“The α1 isoform predominates in VSMCs, ECs, adipocytes, and monocytes/macrophages, whereas cardiomyocytes express much higher amounts of the α2 isoform.”
The paper relies on this without support.
Aberrant AMPK signaling is involved in the pathogenesis of various cardiovascular diseases, including hypertension, atherosclerosis, and stroke.
“Moreover, aberrant AMPK signaling is involved in the pathogenesis of various CVDs, including hypertension, atherosclerosis, and stroke.”
The paper relies on this without support.
Oxidative stress caused by risk factors represents a major contributor to endothelial dysfunction as a common predisposing condition to atherosclerosis.
“Oxidative stress caused by risk factors represents a major contributor to endothelial dysfunction as a common predisposing condition to atherosclerosis.”
The paper relies on this without support.
UCP2 appears to have a main function of controlling ROS generation in diabetes, obesity, and atherosclerosis.
“It appears that UCP2 has a main function of controlling ROS generation in diabetes, obesity, and atherosclerosis, although it was originally considered as a modulator of nonshivering thermogenesis.”
The paper relies on this without support.
Rapid Ca2+ influx into mitochondrial matrix occurs through the mitochondrial Ca2+ uniporter, a specific channel located at the inner mitochondrial membrane.
“It is well established that rapid Ca2+ influx into mitochondrial matrix occurs through the mitochondrial Ca2+ uniporter (MCU), a specific channel located at the inner mitochondrial membrane.”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“For example, AMPK activators such as metformin and berberine improve mitochondrial efficiency and energy substrate utilization, which can reduce fatigue and increase endurance capacity”
From Exercise-Induced Muscle–Fat Crosstalk: Molecular Mediators and Their Pharmacological Modulation for the Maintenance of Metabolic Flexibility in Aging (2025) · cites this paper as [106]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“For example, metformin and berberine activate AMPK, promoting fatty acid oxidation, mitochondrial biogenesis, and improved insulin sensitivity”
From Exercise-Induced Muscle–Fat Crosstalk: Molecular Mediators and Their Pharmacological Modulation for the Maintenance of Metabolic Flexibility in Aging (2025) · cites this paper as [106]
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
Each contradiction between two passages listed here was confirmed by an independent check.
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 6. Cardio-Metabolic Diseases > 6.1. Diabetes
“Empagliflozin exerted its protective roles via inhibition of AMPK-dependent mitochondrial fission [229].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 6. Cardio-Metabolic Diseases > 6.1. Diabetes
“In the meantime, DRP1-S616 phosphorylation was decreased, while DRP1-S637 phosphorylation was increased, ultimately leading to mitochondrial fission [229].”
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 6. Cardio-Metabolic Diseases > 6.2. Inflammation
“For instance, melatonin protected HUVECs against lipopolysaccharide-mediated apoptosis [140].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 6. Cardio-Metabolic Diseases > 6.2. Inflammation
“Collectively, this study demonstrated that melatonin induced endothelial cell apoptosis through activation of the AMPK-sarcoplasmic/endoplasmic reticulum calcium ATPase 2a pathway under conditions of inflammation [140].”
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 4. AMPK Regulates Mitochondrial Homeostasis > 4.2. AMPK Regulates Mitochondrial Dynamics
“In human bone osteosarcoma epithelial cells (U2OS) and MEFs, AMPK directly phosphorylated MFF on two sites, Ser155 and Ser173 [82,104].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 4. AMPK Regulates Mitochondrial Homeostasis > 4.2. AMPK Regulates Mitochondrial Dynamics
“A further study showed that AMPK-driven MFF phosphorylation at Ser155 and Ser172 is one potential mechanism to account for mitochondrial fission owing to mitochondrial respiration decline [82].”
Citations
Cites
5 retracted
Activation of the AMP-activated Protein Kinase by the Anti-diabetic Drug Metformin in Vivo
Zou, M., Kirkpatrick, S. S., Davis, B. J., Nelson, J. S., Wiles, W. G., Schlattner, U., Neumann, D., Brownlee, M., Freeman, M. B., & Goldman, M. H. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m404421200 · Cited by 480
Self-citationRetractedXie, Z., Zhang, J., Wu, J., Viollet, B., & Zou, M. (2008) · Diabetes · doi:10.2337/db08-0610 · Cited by 165
Self-citationRetractedZhang, J., Xie, Z., Dong, Y., Wang, S., Liu, C., & Zou, M. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m802578200 · Cited by 114
Self-citationRetractedRETRACTED: Redox Regulation of the AMP-Activated Protein Kinase
Han, Y., Wang, Q., Song, P., Zhu, Y., & Zou, M.-H. (2010) · PLoS ONE · doi:10.1371/journal.pone.0015420 · Cited by 71
Self-citationRetractedZou, M.-H., Hou, X., Shi, C., et al. (2019) · Journal of Biological Chemistry · doi:10.1074/jbc.w119.011600 · Cited by 2
Self-citationRetractedJames, S. L., Abate, D., Abate, K. H., Abay, S. M., Abbafati, C., Abbasi, N., Abbastabar, H., Abd-Allah, F., Abdela, J., Abdelalim, A., et al. (2018) · The Lancet · doi:10.1016/s0140-6736(18)32279-7 · Cited by 13,867
Vos, T., Abajobir, A. A., Abate, K. H., Abbafati, C., Abbas, K. M., Abd-Allah, F., Abdulkader, R. S., Abdulle, A. M., Abebo, T. A., Abera, S. F., et al. (2017) · The Lancet · doi:10.1016/s0140-6736(17)32154-2 · Cited by 13,220
AMPK and mTOR regulate autophagy through direct phosphorylation of Ulk1
Kim, J., Kundu, M., Viollet, B., & Guan, K.-L. (2011) · Nature Cell Biology · doi:10.1038/ncb2152 · Cited by 7,227
Mutations in the parkin gene cause autosomal recessive juvenile parkinsonism
Kitada, T., Asakawa, S., Hattori, N., Matsumine, H., Yamamura, Y., Minoshima, S., Yokochi, M., Mizuno, Y., & Shimizu, N. (1998) · Nature · doi:10.1038/33416 · Cited by 5,227
AMPK: a nutrient and energy sensor that maintains energy homeostasis
Hardie, D. G., Ross, F. A., & Hawley, S. A. (2012) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3311 · Cited by 4,602
Cited by
Sorted by citations
Molecular mechanisms of aging and anti-aging strategies
Li, Y., Tian, X., Luo, J., Bao, T., Wang, S., & Wu, X. (2024) · Cell Communication and Signaling · doi:10.1186/s12964-024-01663-1 · Cited by 380
The role of AMPK in macrophage metabolism, function and polarisation
Cui, Y., Chen, J., Zhang, Z., Shi, H., Sun, W., & Yi, Q. (2023) · Journal of Translational Medicine · doi:10.1186/s12967-023-04772-6 · Cited by 213
Targeting oxidative stress as a preventive and therapeutic approach for cardiovascular disease
Yan, Q., Liu, S., Sun, Y., Chen, C., Yang, S., Lin, M., Long, J., Yao, J., Lin, Y.-T., Yi, F., et al. (2023) · Journal of Translational Medicine · doi:10.1186/s12967-023-04361-7 · Cited by 184
Yue, D., Zhang, Q., Zhang, J., Liu, W., Chen, L., Wang, M., Li, R., Qin, S., Song, X., & Ji, Y. (2022) · Environment International · doi:10.1016/j.envint.2022.107706 · Cited by 147
The role of aldehyde dehydrogenase 2 in cardiovascular disease
Zhang, J., Guo, Y., Zhao, X., Pang, J., Pan, C., Wang, J., Wei, S., Yu, X., Zhang, C., Chen, Y., et al. (2023) · Nature Reviews Cardiology · doi:10.1038/s41569-023-00839-5 · Cited by 142
New Dawn for Atherosclerosis: Vascular Endothelial Cell Senescence and Death
Bu, L.-L., Yuan, H., Xie, L., Guo, M.-H., Liao, D., & Zheng, X. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms242015160 · Cited by 133
Mitochondria Related Cell Death Modalities and Disease
Tian, C., Liu, Y., Li, Z., Zhu, P., & Zhao, M. (2022) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2022.832356 · Cited by 113
Li, H., Yang, D., Zhang, Y., Zheng, F., Gao, F., Sun, J., & Shi, G. (2022) · Chinese Medicine · doi:10.1186/s13020-022-00616-5 · Cited by 110
Targeting CRL4 suppresses chemoresistant ovarian cancer growth by inducing mitophagy
Meng, Y., Qiu, L., Zeng, X., Hu, X., Zhang, Y., Wan, X., Mao, X., Wu, J., Xu, Y., Xiong, Q., et al. (2022) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-022-01253-y · Cited by 116
Cardiac cell senescence: molecular mechanisms, key proteins and therapeutic targets
Luan, Y., Zhu, X., Jiao, Y., Liu, H., Huang, Z., Pei, J., Xu, Y., Yang, Y., & Ren, K. (2024) · Cell Death Discovery · doi:10.1038/s41420-023-01792-5 · Cited by 116
Targeting AMPK by Statins: A Potential Therapeutic Approach
Dehnavi, S., Kiani, A., Sadeghi, M., Biregani, A. F., Banach, M., Atkin, S. L., Jamialahmadi, T., & Sahebkar, A. (2021) · Drugs · doi:10.1007/s40265-021-01510-4 · Cited by 107
Goel, S. K., Singh, R. P., Singh, V., Singh, H., Kumari, P., Chopra, H., Sharma, R., Nepovimová, E., Vališ, M., Kuča, K., et al. (2022) · Frontiers in Genetics · doi:10.3389/fgene.2022.1022739 · Cited by 113
IL-25 Induced ROS-Mediated M2 Macrophage Polarization via AMPK-Associated Mitophagy
Tsai, M.-L., Tsai, Y., Lin, Y., Hsu, Y., Chen, Y., Tsai, M.-K., Liao, W., Lin, Y.-C., & Hung, C. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms23010003 · Cited by 101
Mitochondrial Dysfunction in Vascular Wall Cells and Its Role in Atherosclerosis
Salnikova, D. I., Orekhova, V. A., Grechko, A. V., Starodubova, A. V., Bezsonov, E. E., Попкова, Т. В., & Orekhov, A. N. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22168990 · Cited by 93
Yin, K., Lu, H., Zhang, Y., Hou, L., Meng, X., Li, J., Zhao, H., & Xing, M. (2022) · Chemico-Biological Interactions · doi:10.1016/j.cbi.2022.110180 · Cited by 89
Yan, Y., Li, M., Lin, J., Ji, Y., Wang, K., Yan, D., Shen, Y., Wang, W., Huang, Z., Jiang, H., et al. (2022) · Frontiers in Pharmacology · doi:10.3389/fphar.2022.947387 · Cited by 84
Matar, D. B., Zhra, M., Nassar, W. K., Altemyatt, H., Naureen, A., Abotouk, N., Elahi, M. A., & Aljada, A. (2025) · Frontiers in Endocrinology · doi:10.3389/fendo.2025.1592683 · Cited by 93
Palabıyık, A. A., & Palabıyık, E. (2025) · Molecular Biology Reports · doi:10.1007/s11033-025-10368-8 · Cited by 76
Youssef, M. E., El-Fattah, E. E. A., Abdelhamid, A. M., Eissa, H., El-Ahwany, E. G., Amin, N. A., Hetta, . F., Mahmoud, M. H., Batiha, G. E., Gobba, N. A., et al. (2021) · Frontiers in Pharmacology · doi:10.3389/fphar.2021.719984 · Cited by 63
Cai, W., Cheng, J., Zong, S.-Y., Yu, Y., Wang, Y., Song, Y., He, R., Yuan, S., Chen, T., Hu, M., et al. (2021) · Molecular Immunology · doi:10.1016/j.molimm.2021.10.007 · Cited by 60
Cao, S., Xiao, H., Li, X., Zhu, J., Gao, J., Wang, L., & Hu, C. (2021) · Antioxidants · doi:10.3390/antiox10122010 · Cited by 58
Autophagy in sarcopenia: Possible mechanisms and novel therapies
Xie, G., Jin, H., Mikhail, H., Pavel, V., Yang, G., Ji, B., Lu, B., & Li, Y. (2023) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2023.115147 · Cited by 62
Proteome characterisation of extracellular vesicles isolated from heart
Claridge, B., Rai, A., Fang, H., Matsumoto, A., Luo, J., McMullen, J. R., & Greening, D. W. (2021) · PROTEOMICS · doi:10.1002/pmic.202100026 · Cited by 58
Exosomes in Cardiovascular Disease: From Mechanism to Therapeutic Target
Reiss, A. B., Ahmed, S., Johnson, M., Saeedullah, U., & Leon, J. D. (2023) · Metabolites · doi:10.3390/metabo13040479 · Cited by 54
Common methods in mitochondrial research (Review)
Yin, Y., & Shen, H. (2022) · International Journal of Molecular Medicine · doi:10.3892/ijmm.2022.5182 · Cited by 52
Zhuo, C., Xin, J., Huang, W., Zhang, D., Yan, X., Li, R., Li, H., Lan, J., Lin, L., Li, L., et al. (2023) · Toxicology · doi:10.1016/j.tox.2023.153597 · Cited by 45
Self-citationHan, H., Li, X., Guo, Y., Zheng, M., Xue, T., & Wang, L. (2021) · Food & Function · doi:10.1039/d0fo02623a · Cited by 43
Humanin and Its Pathophysiological Roles in Aging: A Systematic Review
Coradduzza, D., Congiargiu, A., Chen, Z., Cruciani, S., Zinellu, A., Carru, C., & Medici, S. (2023) · Biology · doi:10.3390/biology12040558 · Cited by 46
Guo, K., & Lü, Y. (2024) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2024.1388759 · Cited by 47
Stimulation of AMPK Prevents Diabetes‐Induced Photoreceptor Cell Degeneration
Song, S., Bao, S., Zhang, C., et al. (2021) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2021/5587340 · Cited by 42
Zhang, Y., Liu, S., Cao, D., Zhao, M., Lu, H., & Wang, P. (2024) · Journal of Ethnopharmacology · doi:10.1016/j.jep.2024.119285 · Cited by 48
Paskeh, M. D. A., Asadi, A., Mirzaei, S., Hashemi, M., Entezari, M., Raesi, R., Hushmandi, K., Zarrabi, A., Ertaş, Y. N., Aref, A. R., et al. (2022) · Cellular Signalling · doi:10.1016/j.cellsig.2022.110323 · Cited by 41
Tero-Vescan, A., Degens, H., Matsakas, A., Ștefănescu, R., Ősz, B. E., & Slevin, M. (2025) · Pharmaceuticals · doi:10.3390/ph18081222 · Cited by 44
“For example, AMPK activators such as metformin and berberine improve mitochondrial efficiency and energy substrate utilization, which can reduce fatigue and increase endurance capacity [106,107].”
Mitochondrial dysfunction in oocytes: implications for fertility and ageing
Wang, T., Xu, P., Yuan, J., Chen, H., Guo, X., Gao, J., Wang, Y., Yao, D., Li, X., Liu, B., et al. (2025) · Journal of Ovarian Research · doi:10.1186/s13048-025-01764-6 · Cited by 47
Metabolic syndrome: molecular mechanisms and therapeutic interventions
Zheng, L., Zeng, A., Liu, L., Tian, W., Wang, R., Zhang, L., Hua, H., & Zhao, J. (2025) · Molecular Biomedicine · doi:10.1186/s43556-025-00303-5 · Cited by 48
Why is endothelial resilience key to maintain cardiac health?
Tombor, L., & Dimmeler, S. (2022) · Basic Research in Cardiology · doi:10.1007/s00395-022-00941-8 · Cited by 36
Visitchanakun, P., Kaewduangduen, W., Charoensappakit, A., Susantitaphong, P., Pisitkun, P., Ritprajak, P., Townamchai, N., & Leelahavanichkul, A. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms222111450 · Cited by 40
AMPK and Pulmonary Hypertension: Crossroads Between Vasoconstriction and Vascular Remodeling
Zhao, Q., Song, P., & Zou, M. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.691585 · Cited by 37
Self-citationZhong, P., Peng, J., Hu, Y., Zhang, J., & Shen, C. (2022) · Journal of Cellular and Molecular Medicine · doi:10.1111/jcmm.17551 · Cited by 34
Li, X., Chen, W., Jia, Z., Xiao, Y., Shi, A., & Ma, X. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26094256 · Cited by 45
Isop, L. M., Neculau, A. E., Necula, R. D., Kakucs, C., Moga, M., & Dima, L. (2023) · Pharmaceuticals · doi:10.3390/ph16121714 · Cited by 36
Exercise training attenuates angiotensin II-induced cardiac fibrosis by reducing POU2F1 expression
Feng, N., Yu, H., Wang, Y., Zhang, Y., Han, X., & Gao, W. D. (2022) · Journal of sport and health science/Journal of Sport and Health Science · doi:10.1016/j.jshs.2022.10.004 · Cited by 33
Exploring Stressors: Impact on Cellular Organelles and Implications for Cellular Functions
Zayani, Z., Matinahmadi, A., Tavakolpournegari, A., & Bidooki, S. H. (2025) · Stresses · doi:10.3390/stresses5020026 · Cited by 35
Guo, Z., Chen, X., Huang, Z., Chen, D., Li, M., Yu, B., He, J., Luo, Y., Yan, H., & Zheng, P. (2022) · Food & Function · doi:10.1039/d1fo03391c · Cited by 33
Exercise-driven cellular autophagy: A bridge to systematic wellness
Zhou, X.-H., Luo, Y., & Yao, X. (2025) · Journal of Advanced Research · doi:10.1016/j.jare.2024.12.036 · Cited by 35
Liang, Y., Chu, P. H., Tian, L., Ho, K., Ip, M., & Mak, J. (2021) · Environmental Pollution · doi:10.1016/j.envpol.2021.118720 · Cited by 31
Wu, Q., Li, D., Huang, C., Zhang, G., Wang, Z., Liu, J., Yu, H., Song, B., Zhang, N., Li, B., et al. (2022) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2022.113517 · Cited by 32
SGLT2 inhibitors and AMPK: The road to cellular housekeeping?
Safaie, N., Masoumi, S., Alizadeh, S., Mirzajanzadeh, P., Nejabati, H. R., Hajiabbasi, M., Alivirdiloo, V., Basmenji, N. C., Radvar, A. D., Majidi, Z., et al. (2024) · Cell Biochemistry and Function · doi:10.1002/cbf.3922 · Cited by 32
Targeting mitochondrial dynamics and redox regulation in cardiovascular diseases
Beg, M. A., Huang, M., Vick, L., Rao, K. N. S., Zhang, J., & Chen, Y. (2024) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2024.02.001 · Cited by 31
Luan, P., Zhang, H., Chen, X., Zhu, Y., Hu, G., Cai, J., & Zhang, Z. (2022) · Ecotoxicology and Environmental Safety · doi:10.1016/j.ecoenv.2022.113276 · Cited by 30
Zhu, J., Chen, H., Guo, J., Zha, C., & Lu, D. (2022) · Journal of Inflammation Research · doi:10.2147/jir.s386470 · Cited by 30
Laurindo, L. F., Rodrigues, V. D., Laurindo, L. F., Cherain, L. M. A., de Lima, E. P., Boaro, B. L., Oliveira, J. D. S. C., Chagas, E. F. B., Catharin, V. C. S., Haber, J. F. D. S., et al. (2024) · Life Sciences · doi:10.1016/j.lfs.2024.123230 · Cited by 31
Chaanine, A. H. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms221910579 · Cited by 31
Afzal, O., Altamimi, A. S. A., Mubeen, B., Alzarea, S. I., Almalki, W. H., Al-Qahtani, S. D., Atiya, E. M., Al-Abbasi, F. A., Ali, F., Ullah, I., et al. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms232012470 · Cited by 36
Tang, J. Y., Chen, Y., Li, J., Yan, S., Wang, Z., Deng, X., Feng, K., Zhang, Y., Chen, C., Geng, H., et al. (2023) · CNS Neuroscience & Therapeutics · doi:10.1111/cns.14198 · Cited by 28
Yu, H., Hong, X., Liu, L., Wu, Y., Xie, X., Fang, G., & Zhi, S. (2021) · Frontiers in Pharmacology · doi:10.3389/fphar.2021.754005 · Cited by 35
Adiponectin receptor agonist AdipoRon modulates human and mouse platelet function
Zhou, X., Cheng, Z., Meng, L. M., Lin, W.-Y., Luo, L., Ming, Z., & Hu, Y. (2022) · Acta Pharmacologica Sinica · doi:10.1038/s41401-022-00943-1 · Cited by 27
Gu, Y., Bai, J., Zhang, J., Zhao, Y., Pan, R., Dong, Y., Cui, H., & Xiao, X. (2022) · Food Research International · doi:10.1016/j.foodres.2022.111285 · Cited by 28
From Kinases to Diseases: Investigating the Role of AMPK in Human Pathologies
Rey, V., & Tamargo‐Gómez, I. (2023) · Kinases and Phosphatases · doi:10.3390/kinasesphosphatases1030012 · Cited by 29
Wang, Y., Li, X., Xu, X., Qu, X., & Yang, Y. (2022) · Journal of Cardiovascular Pharmacology · doi:10.1097/fjc.0000000000001301 · Cited by 28
Zhou, Z., Zhao, Q., Huang, Y., Meng, S., Chen, X., Zhang, G., Chi, Y., Xu, D., Yin, Z., Jiang, H., et al. (2024) · Journal of Cellular and Molecular Medicine · doi:10.1111/jcmm.18407 · Cited by 24
Zhang, Y., Jiang, X., Wang, W., Lei, L., Sheng, R., Li, S., Luo, J., Liu, H., Zhang, J., Han, X., et al. (2024) · Arteriosclerosis, Thrombosis, and Vascular Biology · doi:10.1161/atvbaha.124.321076 · Cited by 27
Xiong, J., Dong, X., Li, S., Jiang, F., Chen, J., Yu, S., Dong, B., & Su, Q. (2021) · Frontiers in Physiology · doi:10.3389/fphys.2021.657378 · Cited by 25
The Hormetic Effect of Metformin: “Less Is More”?
Panfoli, I., Puddu, A., Bertola, N., Ravera, S., & Maggi, D. C. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22126297 · Cited by 29
Melnik, B. C., & Schmitz, G. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms231911503 · Cited by 27
Liu, D., Ding, J., Li, Z., & Lu, Y. (2023) · Cell Biology International · doi:10.1002/cbin.12090 · Cited by 26
Molecular mechanisms of metabolic dysregulation in diabetic cardiomyopathy
Zeng, Y., Li, Y., Jiang, W., & Hou, N. (2024) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2024.1375400 · Cited by 26
Singh, S. K., Yadav, P., Patel, D., Tanwar, S. S., Sherawat, A., Khurana, A., Bhatti, J. S., & Navik, U. (2024) · Environmental Toxicology · doi:10.1002/tox.24291 · Cited by 25
Liu, Y., Shu, J., Liu, T., Xie, J., Li, T., Li, H., & Li, L. (2022) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2022.175365 · Cited by 25
Liu, C., Guo, X., Zhou, Y., & Wang, H. (2023) · Journal of Inflammation Research · doi:10.2147/jir.s441597 · Cited by 25
Yang, H., Wang, Y., Zhen, S., et al. (2023) · Acta Biochimica et Biophysica Sinica · doi:10.3724/abbs.2023039 · Cited by 22
An update in toxicology of ageing
Račková, L., Mach, M., & Brnoliaková, Z. (2021) · Environmental Toxicology and Pharmacology · doi:10.1016/j.etap.2021.103611 · Cited by 22
Tian, J., Zheng, Y., Mou, T., Yun, M., Tian, Y., Lu, Y., Bai, Y., Zhou, Y., Hacker, M., Zhang, X., et al. (2022) · European Journal of Nuclear Medicine and Molecular Imaging · doi:10.1007/s00259-022-06008-z · Cited by 25
Nrf2/Keap1/ARE regulation by plant secondary metabolites: a new horizon in brain tumor management
Dewanjee, S., Bhattacharya, H., Bhattacharyya, C., Chakraborty, P., Fleishman, J. S., Alexiou, A. T., Papadakis, M., & Jha, S. K. (2024) · Cell Communication and Signaling · doi:10.1186/s12964-024-01878-2 · Cited by 29
Bioactive potential of punicalagin: A comprehensive review
Shabir, I., Dar, A. H., Dash, K. K., Manzoor, S., Srivastava, S., Pandey, V. K., Shams, R., Bashir, I., Khan, S. A., Mukarram, S. A., et al. (2024) · Applied Food Research · doi:10.1016/j.afres.2024.100572 · Cited by 21
Hassanpour, P., Sadeghsoltani, F., Saghebasl, S., Boroumand, S., Khanicheragh, P., Tafti, S. H. A., Rahbarghazi, R., & Rahmati, M. (2025) · Stem Cell Research & Therapy · doi:10.1186/s13287-025-04193-w · Cited by 22
Toll-Like Receptor 4 (TLR4) and AMPK Relevance in Cardiovascular Disease
Vaez, H., Soraya, H., Garjani, A., & Gholikhani, T. (2021) · Advanced Pharmaceutical Bulletin · doi:10.34172/apb.2023.004 · Cited by 23
Hu, Y., Gu, X., Zhang, Y., Ma, W., Sun, L., Wang, C., & Ren, B. (2023) · Environmental Toxicology · doi:10.1002/tox.23958 · Cited by 22
Sung, J. Y., Kim, S. G., Park, S., Kim, J., & Choi, H. C. (2024) · Experimental & Molecular Medicine · doi:10.1038/s12276-024-01297-w · Cited by 25
Deng, Z., Yang, Z., & Peng, J. (2021) · Critical Reviews in Food Science and Nutrition · doi:10.1080/10408398.2021.1992606 · Cited by 21
Epicardial Adipose Tissue as an Independent Cardiometabolic Risk Factor for Coronary Artery Disease
Karampetsou, N., Alexopoulos, L. G., Minia, A., Pliaka, V., Tsolakos, N., Kontzoglou, K., Perrea, D. N., & Patapis, P. (2022) · Cureus · doi:10.7759/cureus.25578 · Cited by 20
Viloria, M. A. D., Li, Q., Lu, W., Nhu, N. T., Liu, Y., Cui, Z.-Y., Cheng, Y., & Lee, S. (2022) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2022.949744 · Cited by 20
Seksaria, S., Mehan, S., Dutta, B. J., Gupta, G. D., Ganti, S. S., & Singh, A. (2023) · Journal of Biochemical and Molecular Toxicology · doi:10.1002/jbt.23330 · Cited by 23
Isoform-specific roles of AMP-activated protein kinase in cardiac physiology and pathophysiology
Rakoubian, A., Khinchin, J., Yarbro, J. R., Kobayashi, S., & Liang, Q. (2025) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2025.1638515 · Cited by 25
Mahmoudi, A. A., Butler, A. E., Jamialahmadi, T., & Sahebkar, A. (2021) · BioMed Research International · doi:10.1155/2021/3654660 · Cited by 20
Yang, L., Chen, X., Chen, D., Yu, B., He, J., Luo, Y., Zheng, P., Chen, H., Yan, H., & Huang, Z. (2023) · The Journal of Nutritional Biochemistry · doi:10.1016/j.jnutbio.2023.109327 · Cited by 20
Sexual Dimorphism in Cardiometabolic Diseases: The Role of AMPK
Kvandová, M., Púzserová, A., & Bališ, P. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms241511986 · Cited by 20
Exercise Improves Heart Function after Myocardial Infarction: The Merits of AMPK
Zhang, X., Zhao, Y., Guo, D., Luo, M., Zhang, Q., Zhang, L., & Zhang, D. (2024) · Cardiovascular Drugs and Therapy · doi:10.1007/s10557-024-07564-2 · Cited by 20
Efentakis, P., Psarakou, G., Varela, A., Papanagnou, E., Chatzistefanou, M., Nikolaou, P., Davos, C. H., Gavriatopoulou, M., Trougakos, I. P., Dimopoulos, M. A., et al. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms222010956 · Cited by 18
Shi, B., Liu, S., Huang, A., et al. (2021) · Evidence-based Complementary and Alternative Medicine · doi:10.1155/2021/4451779 · Cited by 18
Chen, Z., Zhang, W., Wu, M., Huang, H., Zou, L., & Luo, Q. (2021) · Bioengineered · doi:10.1080/21655979.2021.1993717 · Cited by 18
Kong, L., Liu, Y., Wang, J., Lv, M.-J., Wang, Y.-Z., Sun, W., Cao, H., Guo, R., Zhang, L., Yu, Y., et al. (2025) · Phytomedicine · doi:10.1016/j.phymed.2025.156529 · Cited by 19
Han, X., Zheng, R., Zhang, J., Liu, Y., Li, Z., Liu, G., Zheng, J., Li, W., Liang, Z.-J., Wang, M., et al. (2025) · Nature Communications · doi:10.1038/s41467-025-61901-z · Cited by 18
Yang, Q., Ma, Q., Xu, J., Liu, Z., Zou, J., Shen, J., Zhou, Y., Da, Q., Mao, X., Lu, S., et al. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2020.611354 · Cited by 18
Sun, X. H., Han, Y., Dong, C., Qu, H., Yu, Y., Ju, J., Bai, Y., & Yang, B. (2022) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2022.113162 · Cited by 18
Suksawad, N., Udompornpitak, K., Thawinpipat, N., Korwattanamongkol, P., Visitchanakun, P., Phuengmaung, P., Saisorn, W., Kueanjinda, P., & Leelahavanichkul, A. (2023) · Biomedicines · doi:10.3390/biomedicines11041208 · Cited by 17
Mitochondrial Kinase Signaling for Cardioprotection
Boengler, K., Eickelmann, C., & Kleinbongard, P. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25084491 · Cited by 17
Jiang, S., Huang, C., Wang, S., et al. (2022) · BioMed Research International · doi:10.1155/2022/4293265 · Cited by 16
Deng, X., Luo, H., He, J., Deng, W., & Wang, D. (2024) · Clinical and Experimental Hypertension · doi:10.1080/10641963.2024.2332695 · Cited by 17
Effects of SGLT2 inhibitors on ion channels in heart failure: focus on the endothelium
Wang, M., Preckel, B., Zuurbier, C. J., & Weber, N. C. (2025) · Basic Research in Cardiology · doi:10.1007/s00395-025-01115-y · Cited by 20
Metadata
- Authors
- Wu, S., & Zou, M.-H.
- Affiliations
- Georgia State University (US)
- Corresponding author
- Wu, Shengnan
- Venue
- International Journal of Molecular Sciences
- Publisher
- MDPI AG
- Published
- 2020-07-15
- Volume
- 21
- Issue
- 14
- Pages
- 4987
- ISSN
- 1422-0067 (ISSN-L)
- PMC
- PMC7404275
- OpenAlex
- W3043111807
- Cited by
- 286
- References
- 278
- Citations by year
- 2026: 48 · 2025: 71 · 2024: 50 · 2023: 45 · 2022: 43 · 2021: 27 · 2020: 2
- FWCI
- 2.80
- Type
- journal article
- Language
- en
- Open access
- gold
- dx.doi.org
- Licence
- Locations
- International Journal of Molecular Sciences (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- American Heart Association (16POST29960011, 19CDA34760110)
- Georgia Research Alliance
- National Institutes of Health
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Health Sciences › Medicine › Geriatrics and Gerontology › Sirtuins and Resveratrol in Medicine
- Keywords
- AMPK, mitochondrial dysfunction, mitochondrial homeostasis, cardiovascular disease, redox sensing, energy homeostasis, statins, metformin, berberine, polyphenols, resveratrol
- MeSH terms
- Adenosine Triphosphate, Animals, Cardiovascular Diseases, Energy Metabolism, Humans, Mitochondria, Reactive Oxygen Species, AMP-Activated Protein Kinases, Mitochondrial Turnover
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
A language model drew the claims from the paper on 2026-10-09, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).
A second model labelled each claim on 2026-10-09 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
