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
Murphy, M. P. (2009) · Biochemical Journal · doi:10.1042/bj20081386 · Cited by 8,207
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).”
BackgroundSelf-citationYellon, D. M., & Hausenloy, D. J. (2007) · New England Journal of Medicine · doi:10.1056/nejmra071667 · Cited by 3,797
Ischemia and reperfusion—from mechanism to translation
Eltzschig, H. K., & Eckle, T. D. L. G. (2011) · Nature Medicine · doi:10.1038/nm.2507 · Cited by 3,468
Sterile inflammation: sensing and reacting to damage
Chen, G. Y., & Nuñez, G. (2010) · Nature Reviews Immunology · doi:10.1038/nri2873 · Cited by 3,051
Ischaemic accumulation of succinate controls reperfusion injury through mitochondrial ROS
Chouchani, E. T., Pell, V. R., Gaude, E., Aksentijević, D., Sundier, S. Y., Robb, E. L., Logan, A., Nadtochiy, S. M., Ord, E. N. J., Smith, A. C., et al. (2014) · Nature · doi:10.1038/nature13909 · Cited by 2,907
Self-citationMyocardial ischemia-reperfusion injury: a neglected therapeutic target
Hausenloy, D. J., & Yellon, D. M. (2013) · Journal of Clinical Investigation · doi:10.1172/jci62874 · Cited by 2,357
White, H. D., Norris, R. M., Brown, M. A., Brandt, P. W., Whitlock, R. M. L., & Wild, C. J. (1987) · Circulation · doi:10.1161/01.cir.76.1.44 · Cited by 2,348
Succinate links TCA cycle dysfunction to oncogenesis by inhibiting HIF-α prolyl hydroxylase
Selak, M. A., Armour, S. M., MacKenzie, E. D., Boulahbel, H., Watson, D. G., Mansfield, K. D., Pan, Y., Simon, M. C., Thompson, C. B., & Gottlieb, E. (2005) · Cancer Cell · doi:10.1016/j.ccr.2004.11.022 · Cited by 2,108
Reimer, K. A., Lowe, J. E., Rasmussen, M. M., & Jennings, R. B. (1977) · Circulation · doi:10.1161/01.cir.56.5.786 · Cited by 1,944
Cited by
Sorted by citations
Mills, E. L., Kelly, B., Logan, A., Costa, A. S. H., Varma, M., Bryant, C. E., Tourlomousis, P., Däbritz, J. H. M., Gottlieb, E., Latorre, I., et al. (2016) · Cell · doi:10.1016/j.cell.2016.08.064 · Cited by 2,291
Self-citationDefining roles of specific reactive oxygen species (ROS) in cell biology and physiology
Sies, H., Belousov, V. V., Chandel, N. S., Davies, M. J., Jones, D. P., Mann, G. E., Murphy, M. P., Yamamoto, M., & Winterbourn, C. (2022) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-022-00456-z · Cited by 1,735
Self-citationZielonka, J., Joseph, J., Sikora, A., Hardy, M., Ouari, O., Vasquez-Vivar, J., Cheng, G., Lopez, M., & Kalyanaraman, B. (2017) · Chemical Reviews · doi:10.1021/acs.chemrev.7b00042 · Cited by 1,683
The cell biology of mitochondrial membrane dynamics
Giacomello, M., Pyakurel, A., Glytsou, C., & Scorrano, L. (2020) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-020-0210-7 · Cited by 1,550
Mitochondrial electron transport chain, ROS generation and uncoupling (Review)
Zhao, R., Jiang, S., Zhang, L., & Yu, Z. (2019) · International Journal of Molecular Medicine · doi:10.3892/ijmm.2019.4188 · Cited by 1,511
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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