Krieg Lab

ALT Schematic of malonate inhibition of IRI in MI. Ischemia-accumulated succinate is rapidly oxidized on reperfusion by SDH upon reperfusion. This drives the ROS burst at reperfusion via RET at complex I, which subsequently primes cardiomyocytes for cell death and leads to post-MI HF. Malonate inhibits SDH, slowing down succinate oxidation and ROS production on reperfusion, reducing cell death. Malonate entry into cardiomyocytes can be enhanced by ischemia or low pH, driving the entry of monocarboxylate malonate via MCT1. Whether malonate can prevent post-MI HF by preventing RET-ROS on reperfusion is currently unknown. (MCT1 monocarboxylate transporter 1, DIC dicarboxylate carrier, SDH succinate dehydrogenase, CxI complex I, RET reverse electron transport, ROS reactive oxygen species, TCA tricarboxylic acid cycle, EF ejection fraction)