biostudies-literaturePrag HABritish Heart FoundationBarts CharityNational Institute for Health Research Blood and Transplant Research UnitMedical Research CouncilBristol NIHR Biomedical Research CentreNational Institute for Health Research (NIHR)Wellcome Trust Investigator awardWellcome TrustSchool of Biological and Chemical SciencesOrgan Donation and Transplantation PhD studentshipDepartment of Physiology, University of Lausanne, Switzerland and IdEx Bordeaux1188-1201https://www.ebi.ac.uk/biostudies/studies/S-EPMC7983001biostudies-literatureUnknown117(4)<h4>Aims</h4>Succinate accumulates several-fold in the ischaemic heart and is then rapidly oxidized upon reperfusion, contributing to reactive oxygen species production by mitochondria. In addition, a significant amount of the accumulated succinate is released from the heart into the circulation at reperfusion, potentially activating the G-protein-coupled succinate receptor (SUCNR1). However, the factors that determine the proportion of succinate oxidation or release, and the mechanism of this release, are not known.<h4>Methods and results</h4>To address these questions, we assessed the fate of accumulated succinate upon reperfusion of anoxic cardiomyocytes, and of the ischaemic heart both ex vivo and in vivo. The release of accumulated succinate was selective and was enhanced by acidificaCardiovascular researchMechanism of succinate efflux upon reperfusion of the ischaemic heart.PMC7983001RG/17/15/33106MRC_MC_UU_12022/6IG/14/2/30991MR/P000320/1ACF-2018-14-004MC_UU_12022/61620803MRC0215110159/Z/15/ZANR-10-IDEX-03-02MC_U105663142MR/L012723/1MC_UU_00015/3Tronci LShattock MJHuang MMNikitopoulou EBeach TESaeb-Parsy KFrezza CKrieg TAscione RHadjihambi APrag HAYoung TMulvey JFAksentijevic DGruszczyk AVPellerin LMurphy MPJames AMfalseMechanism of succinate efflux upon reperfusion of the ischaemic heart.<h4>Aims</h4>Succinate accumulates several-fold in the ischaemic heart and is then rapidly oxidized upon reperfusion, contributing to reactive oxygen species production by mitochondria. In addition, a significant amount of the accumulated succinate is released from the heart into the circulation at reperfusion, potentially activating the G-protein-coupled succinate receptor (SUCNR1). However, the factors that determine the proportion of succinate oxidation or release, and the mechanism of this release, are not known.<h4>Methods and results</h4>To address these questions, we assessed the fate of accumulated succinate upon reperfusion of anoxic cardiomyocytes, and of the ischaemic heart both ex vivo and in vivo. The release of accumulated succinate was selective and was enhanced by acidifica2021-01-01T00:00:00Z2021 Mar2026-06-12T04:01:09.194Z2022-07-19T15:06:19.806ZS-EPMC79830013276682810.1093/cvr/cvaa148