The DOI matches its Crossref record; 106 of the 106 references it cites were found in a registry or an index.
A Unifying Mechanism for Mitochondrial Superoxide Production during Ischemia-Reperfusion Injury
Open accessAbstract
Ischemia-reperfusion (IR) injury occurs when blood supply to an organ is disrupted--ischemia--and then restored--reperfusion--leading to a burst of reactive oxygen species (ROS) from mitochondria. It has been tacitly assumed that ROS production during IR is a non-specific consequence of oxygen interacting with dysfunctional mitochondria upon reperfusion. Recently, this view has changed, suggesting that ROS production during IR occurs by a defined mechanism. Here we survey the metabolic factors underlying IR injury and propose a unifying mechanism for its causes that makes sense of the huge amount of disparate data in this area and provides testable hypotheses and new directions for therapies.
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In the citing paper
“This type of ROS generation occurs when succinate, the substrate for complex II, is present in high concentration and is responsible in vivo for the ROS generated after ischemia upon reperfusion (171, 172).”
From Sources of Vascular Nitric Oxide and Reactive Oxygen Species and Their Regulation (2019) · cites this paper as [172]
In the citing paper
“SUCNR1 ligation on MoDC or the U937 macrophage cell line induces cell migration, suggesting that succinate can act as a chemokine4.”
From Coupling Krebs cycle metabolites to signalling in immunity and cancer (2018) · cites this paper as [4]
In the citing paper
“Priming of DCs with succinate and antigen simultaneously, elevates antigen-specific T cell activation, increasing TNFα and IFN-γproduction from these cells4.”
From Coupling Krebs cycle metabolites to signalling in immunity and cancer (2018) · cites this paper as [4]
In the citing paper
“SUCNR1 is highly expressed in mouse kidney, liver, spleen, small intestine3, and on dendritic cells (DCs) 4 and ligand binding induces Gi and Gq signalling cascades3.”
From Coupling Krebs cycle metabolites to signalling in immunity and cancer (2018) · cites this paper as [4]
In the citing paper
“Extracellular succinate addition also acts in synergy with TLR ligands to increase TNFα and IL-1β expression4 and increases the capacity of DCs to act as antigen presenting cells.”
From Coupling Krebs cycle metabolites to signalling in immunity and cancer (2018) · cites this paper as [4]
In the citing paper
“one likely role is as an inflammatory signal, acting via SUCNR14,5,161,162.”
From Coupling Krebs cycle metabolites to signalling in immunity and cancer (2018) · cites this paper as [4]
In the citing paper
“Numerous metabolic pathways have been implicated in the metabolic reprogramming of immune cells, in particular those that regulate succinate levels, which, in turn, can influence HIF signaling or other pathways (13,25,40,41).”
From Immunoresponsive Gene 1 and Itaconate Inhibit Succinate Dehydrogenase to Modulate Intracellular Succinate Levels (2016) · cites this paper as [40]
In the citing paper
“Notably, SDH inhibition protected against brain injury after ischemia/reperfusion (40,41), suggesting that inhibition of SDH by endogenously produced itaconate may buffer against potential oxidative damage that can occur under such conditions.”
From Immunoresponsive Gene 1 and Itaconate Inhibit Succinate Dehydrogenase to Modulate Intracellular Succinate Levels (2016) · cites this paper as [40]
Citations
Cites
How mitochondria produce reactive oxygen species
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Self-citationSuccinate is an inflammatory signal that induces IL-1β through HIF-1α
Tannahill, G. M., Curtis, A. M., Adamik, J., Palsson-McDermott, E. M., McGettrick, A. F., Goel, G., Frezza, C., Bernard, N. J., Kelly, B., Foley, N. H., et al. (2013) · Nature · doi:10.1038/nature11986 · Cited by 4,176 · cited 2×
“…probably in conjunction with elevated ROS (Guzy et al., 2008), can stabilize the hypoxia-inducible factors (HIFs) by inhibiting their HIF-α prolyl hydroxylases-mediated degradation, thus leading to activation of a pseudohypoxic response (Selak et al., 2005; Tannahill et al., 2013) (Figure 2).”
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Metadata
- Authors
- Chouchani, E. T., Pell, V. R., James, A. M., Work, L. M., Saeb-Parsy, K., Frezza, C., Krieg, T., & Murphy, M. P.
- Affiliations
- Harvard University (US)
- University of Cambridge (GB)
- MRC Mitochondrial Biology Unit (GB)
- University of Glasgow (GB)
- Corresponding author
- Murphy, Michael P.
- ORCID
- Venue
- Cell Metabolism
- Publisher
- Elsevier BV
- Published
- 2016-02
- Volume
- 23
- Issue
- 2
- Pages
- 254-263
- ISSN
- 1550-4131 (ISSN-L)
- OpenAlex
- W2239083587
- Semantic Scholar
- 05aae81910c5536362646624d7e2848d0da4e591
- Cited by
- 752
- References
- 106
- Citations by year
- 2026: 62 · 2025: 78 · 2024: 63 · 2023: 79 · 2022: 90 · 2021: 104 · 2020: 83 · 2019: 64 · 2018: 58 · 2017: 50 · 2016: 19
- FWCI
- 10.01
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell Metabolism (publishedVersion)
- PubMed (publishedVersion)
- ENLIGHTEN (Jurnal Bimbingan dan Konseling Islam) (acceptedVersion)
- Apollo (University of Cambridge) (submittedVersion, cc-by-nc-nd)
- Funders
- British Heart Foundation
- Medical Research Council (MC_UU_12022/6)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac Ischemia and Reperfusion
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Keywords
- ischemia-reperfusion injury, mitochondrial superoxide production, reactive oxygen species, mitochondrial dysfunction, reperfusion, oxidative stress, metabolic factors, tissue damage
- MeSH terms
- Animals, Electron Transport, Humans, Mitochondria, Models, Biological, Sulfhydryl Compounds, Superoxides, Reperfusion Injury
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