How does mitochondrial Ca2+ change during ischemia and reperfusion? Implications for activation of the permeability transition pore.

J Gen Physiol

Unit of Cardiac Physiology, Division of Cardiovascular Sciences, University of Manchester, Manchester, UK.

Published: January 2025

Cardiac ischemia followed by reperfusion results in cardiac cell death, which has been attributed to an increase of mitochondrial Ca2+ concentration, resulting in activation of the mitochondrial permeability transition pore (PTP). Evaluating this hypothesis requires understanding of the mechanisms responsible for control of mitochondrial Ca2+ in physiological conditions and how they are altered during both ischemia and reperfusion. Ca2+ influx is thought to occur through the mitochondrial Ca2+ uniporter (MCU). However, with deletion of the MCU, an increase in mitochondrial Ca2+ still occurs, suggesting an alternative Ca2+ influx mechanism during ischemia. There is less certainty about the mechanisms responsible for Ca2+ efflux, with contributions from both Ca2+/H+ exchange and a Na+-dependent Ca2+ efflux pathway. The molecular details of both mechanisms are not fully resolved. We discuss this and the contributions of both pathways to the accumulation of mitochondrial Ca2+ during ischemia and reperfusion. We further discuss the role of mitochondrial Ca2+ in activation of the PTP.

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Source
http://dx.doi.org/10.1085/jgp.202313520DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11657230PMC

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