ArticleCell reports2018
Accumulation of Succinate in Cardiac Ischemia Primarily Occurs via Canonical Krebs Cycle Activity.
Article in Cell reports, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 122 papers.
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Who cites it
122 citing papers in PubMed, 197 citations in OpenAlex.
- Spontaneous reperfusion enhances succinate concentration in peripheral blood from stemi patients but its levels does not correlate with myocardial infarct size or area at risk.Scientific reports · 2023Trial
- Aglycemia triggers alternative electron transport to sustain mesenchymal stem cell survival under anoxia.Redox biology · 2026Article
- Succinate and lactate produced as conserved biomarkers through chronic and transient substrate-level phosphorylation: from microorganisms to cancer.Journal of bioenergetics and biomembranes · 2026Review
- Review
- Mechanisms Involved in Pathological Succinate-Mediated Signaling.International journal of molecular sciences · 2026Review
- Mitochondrial succinate transport is required for cardiac ischaemia/reperfusion injury.Cardiovascular research · 2026Article
- Review
- Metabolic rewiring through succinate-GPR91 signaling: a fresh perspective on HFpEF energetics.Cardiovascular diabetology · 2026Article
- Lessons, connections, hypotheses and predictions from protein film electrochemistry.Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry · 2026Review
- A perspective on the future of heart failure research.Journal of molecular and cellular cardiology plus · 2026Article
- Succinylation: A Functional Nexus Between Metabolic Reprogramming and Epigenetic Modifications in Cancer.Molecules (Basel, Switzerland) · 2026Review
- Tricarboxylic acid cycle metabolite index predicts adverse outcomes in acute myocardial infarction patients.BMC medicine · 2026Article
- Metabolic Vulnerabilities as a Therapeutic Target in Breast Cancer.Current oncology (Toronto, Ont.) · 2026Review
- Molecular and Cellular Mechanisms of Myocardial Ischemia and Reperfusion Injury: A Narrative Review.Cells · 2026Review
- Article
- Plasma and pericardial fluid metabolomic signatures of patients with ischemic heart disease.Communications medicine · 2026Article
- SCFAs' pleiotropic role in pathogenesis and salutogenesis: mechanisms in exacerbation and regulation of inflammation and fibrosis from gut to host.Journal of medical microbiology · 2026Review
- Dimethyl malonate suppresses succinate dehydrogenase to alleviate ischemia/reperfusion-induced acute lung injury.Frontiers in pharmacology · 2026Article
- Succinate-mediated metabolic alterations and signaling in RA: mechanisms and therapeutic implications.Frontiers in immunology · 2026Review
- Immune and metabolic signatures characterise constipation-driven endophenotypes in Parkinson's disease.NPJ Parkinson's disease · 2025Article
62 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Succinate accumulates during ischemia, and its oxidation at reperfusion drives injury. The mechanism of ischemic succinate accumulation is controversial and is proposed to involve reversal of mitochondrial complex II. Herein, using stable-isotope-resolved metabolomics, we demonstrate that complex II reversal is possible in hypoxic mitochondria but is not the primary succinate source in hypoxic cardiomyocytes or ischemic hearts. Rather, in these intact systems succinate primarily originates from canonical Krebs cycle activity, partly supported by aminotransferase anaplerosis and glycolysis from glycogen. Augmentation of canonical Krebs cycle activity with dimethyl-α-ketoglutarate both increases ischemic succinate accumulation and drives substrate-level phosphorylation by succinyl-CoA synthetase, improving ischemic energetics. Although two-thirds of ischemic succinate accumulation is extracellular, the remaining one-third is metabolized during early reperfusion, wherein acute complex II inhibition is protective. These results highlight a bifunctional role for succinate: its complex-II-independent accumulation being beneficial in ischemia and its complex-II-dependent oxidation being detrimental at reperfusion.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.