The role of succinate and ROS in reperfusion injury – A critical appraisal

• Published in: Journal of molecular and cellular cardiology Vol. 110; pp. 1 - 14
• Main Authors: Andrienko, Tatyana N., Pasdois, Philippe, Pereira, Gonçalo C., Ovens, Matthew J., Halestrap, Andrew P.
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.09.2017; Academic Press
• Subjects: Animals; Calcium; Electron Transport Complex I - metabolism; Heart; Hexokinase; Humans; Ischemia/reperfusion injury; Mitochondria; Mitochondria, Heart - metabolism; Mitochondrial Membrane Transport Proteins - metabolism; Mitochondrial Permeability Transition Pore; Myocardial Reperfusion Injury - metabolism; Permeability transition pore; Reactive oxygen species; Reactive Oxygen Species - metabolism; Succinate; Succinic Acid - metabolism; Bcl-2; DHE; Heart; Reactive oxygen species; HK; Ischemia/reperfusion injury; Calcium; BCECF; ANT; LS; pmf; Mdivi-1; mPTP; 5-cH2DCFDA; G-6-P; Drp1; Mitochondria; PO1; Permeability transition pore; Bid; PCr; CrP; Bad; NCLX; Succinate; IP; CK; IMM; PKCε; IR; SOD; Bak; OMM; Hexokinase; CsA; GSK3β; Bcl-xL; REF; MitoPY1; IF1; ROS; Bax; VDAC; Cyp-D; MCU

We critically assess the proposal that succinate-fuelled reverse electron flow (REF) drives mitochondrial matrix superoxide production from Complex I early in reperfusion, thus acting as a key mediator of ischemia/reperfusion (IR) injury. Real-time surface fluorescence measurements of NAD(P)H and fl...