The DOI matches its Crossref record; 33 of the 33 references it cites were found in a registry or an index.
A Redox-Dependent Mechanism for Regulation of AMPK Activation by Thioredoxin1 during Energy Starvation
Open accessAbstract
5'-AMP-activated protein kinase (AMPK) is a key regulator of metabolism and survival during energy stress. Dysregulation of AMPK is strongly associated with oxidative-stress-related disease. However, whether and how AMPK is regulated by intracellular redox status remains unknown. Here we show that the activity of AMPK is negatively regulated by oxidation of Cys130 and Cys174 in its α subunit, which interferes with the interaction between AMPK and AMPK kinases (AMPKK). Reduction of Cys130/Cys174 is essential for activation of AMPK during energy starvation. Thioredoxin1 (Trx1), an important reducing enzyme that cleaves disulfides in proteins, prevents AMPK oxidation, serving as an essential cofactor for AMPK activation. High-fat diet consumption downregulates Trx1 and induces AMPK oxidation, which enhances cardiomyocyte death during myocardial ischemia. Thus, Trx1 modulates activation of the cardioprotective AMPK pathway during ischemia, functionally linking oxidative stress and metabolism in the heart.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
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?
In the citing paper
“HFD-induced AMPK deficiency contributed to the enhanced cardiomyocyte death in myocardial ischemia [267].”
From AMPK, Mitochondrial Function, and Cardiovascular Disease (2020) · cites this paper as [267]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
2 retracted
Cao, C., Lü, S., Kivlin, R., Wallin, B., Card, E., Bagdasarian, A., Tamakloe, T., Chu, W., Guan, K., & Wan, Y. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m804144200 · Cited by 104
RetractedRETRACTED: 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
RetractedMammalian thioredoxin is a direct inhibitor of apoptosis signal‐regulating kinase (ASK) 1
Saitoh, M., Nishitoh, H., Fujii, M., Takeda, K., Tobiume, K., Sawada, Y., Kawabata, M., Miyazono, K., & Ichijo, H. (1998) · The EMBO Journal · doi:10.1093/emboj/17.9.2596 · Cited by 2,377
Oxidant signals and oxidative stress
Finkel, T. (2003) · Current Opinion in Cell Biology · doi:10.1016/s0955-0674(03)00002-4 · Cited by 1,393
Hawley, S. A., Davison, M., Woods, A., Davies, S. P., Beri, R. K., Carling, D., & Hardie, D. G. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.44.27879 · Cited by 1,264
Mustacich, D. J., & Powis, G. (2000) · Biochemical Journal · doi:10.1042/bj3460001 · Cited by 838
Russell, R. R., Li, J., Coven, D. L., Pypaert, M., Zechner, C., Palmeri, M., Giordano, F. J., Mu, J., Birnbaum, M. J., & Young, L. H. (2004) · Journal of Clinical Investigation · doi:10.1172/jci19297 · Cited by 738
Thioredoxin and Related Molecules–From Biology to Health and Disease
Lillig, C. H., & Holmgren, A. (2007) · Antioxidants & Redox Signaling · doi:10.1089/ars.2007.9.25 · Cited by 724
AMPK is a direct adenylate charge-regulated protein kinase
Oakhill, J. S., Steel, R., Chen, Z.-P., Scott, J. W., Ling, N., Tam, S., & Kemp, B. E. (2011) · Science · doi:10.1126/science.1200094 · Cited by 612
Aging-associated reductions in AMP-activated protein kinase activity and mitochondrial biogenesis
Reznick, R. M., Zong, H., Li, J., Morino, K., Moore, I. K., Yu, H. J., Liu, Z.-X., Dong, J., Mustard, K. J., Hawley, S. A., et al. (2007) · Cell Metabolism · doi:10.1016/j.cmet.2007.01.008 · Cited by 555
Cited by
Sorted by citations
AMPK: Mechanisms of Cellular Energy Sensing and Restoration of Metabolic Balance
Garcia, D., & Shaw, R. J. (2017) · Molecular Cell · doi:10.1016/j.molcel.2017.05.032 · Cited by 2,061
Mechanisms of physiological and pathological cardiac hypertrophy
Nakamura, M., & Sadoshima, J. (2018) · Nature Reviews Cardiology · doi:10.1038/s41569-018-0007-y · Cited by 1,709
Regulation and function of AMPK in physiology and diseases
Jeon, S. (2016) · Experimental & Molecular Medicine · doi:10.1038/emm.2016.81 · Cited by 1,149
ROS-dependent signal transduction
Reczek, C. R., & Chandel, N. S. (2014) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2014.09.010 · Cited by 877
ROS and redox signaling in myocardial ischemia-reperfusion injury and cardioprotection
Cadenas, S. (2018) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2018.01.024 · Cited by 832
Metadata
- Authors
- Shao, D., Oka, S.-I., Liu, T., Zhai, P., Ago, T., Sciarretta, S., Li, H., & Sadoshima, J.
- Affiliations
- Rutgers Health (US)
- Corresponding author
- Sadoshima, Junichi
- Venue
- Cell Metabolism
- Publisher
- Elsevier BV
- Published
- 2014-02
- Volume
- 19
- Issue
- 2
- Pages
- 232-245
- ISSN
- 1550-4131 (ISSN-L)
- PMC
- PMC3937768
- OpenAlex
- W1980239332
- Cited by
- 252
- References
- 32
- Citations by year
- 2026: 21 · 2025: 18 · 2024: 17 · 2023: 14 · 2022: 19 · 2021: 39 · 2020: 22 · 2019: 24 · 2018: 20 · 2017: 18 · 2016: 18 · 2015: 12 · 2014: 10
- FWCI
- 7.92
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell Metabolism (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- IRIS Research product catalog (Sapienza University of Rome) (submittedVersion)
- Funders
- National Institutes of Health
- U.S. Public Health Service
- National Institute on Aging (AG23039, R01AG023039)
- National Heart, Lung, and Blood Institute (HL91469, R01HL067724, HL102738, R01HL102738, R01HL112330, HL-67724, R01HL091469, HL112330)
- National Institute of Neurological Disorders and Stroke (NS 046593, P30NS046593)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac Ischemia and Reperfusion
- Keywords
- AMPK activation, redox regulation, cysteine oxidation, energy starvation, oxidative stress, high-fat diet, cardiomyocyte death, myocardial ischemia, myocardial metabolism, disulfide bond reduction
- MeSH terms
- Animals, Mice, Transgenic, Models, Biological, Oxidation-Reduction, Phosphorylation, Mass Spectrometry, Thioredoxins, Immunoblotting, Immunoprecipitation, Mice, AMP-Activated Protein Kinases
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.
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
