Mitochondria rescue cells from ischemic injury

SUSANA CADENAS

DOI: 10.1126/science.add4629

Abstract

Ischemic diseases, such as myocardial infarction and stroke, are major causes of death worldwide. To date, therapies aimed at preventing ischemic damage or restoring functional tissue have not been successful. Kynurenic acid (KynA), a metabolite of tryptophan metabolism, is tissue protective in cardiac, cerebral, renal, and retinal models of ischemia, but the mechanism of this protection was unknown. On page 621 of this issue, Wyant et al. (1) report that KynA binds G protein–coupled receptor 35 (GPR35) to activate downstream signaling and, once internalized, indirectly interacts with adenosine triphosphate (ATP) synthase inhibitory factor 1 (IF1) to block ATP depletion during ischemia by promoting the dimerization and inactivation of ATP synthase. This cardioprotective mechanism could be further explored for preventing or treating ischemic injury.

https://www.science.org/doi/10.1126/science.add4629