The mitochondria is a major hub for cellular Ca 2+ signaling. The identification of MCU, the mitochondrial Ca 2+ influx mediator, and the mitochondrial Ca 2+ extruder NCLX, were major breakthroughs in this field. Their identification provided novel molecular tools and animal models to interrogate their physiological function and mode of regulation. Here we will focus on the mitochondrial Na + / Ca 2+ exchanger NCLX that plays a dual role in mitochondrial Na + and Ca 2+ signaling. We will discuss recent advances in NCLX mods of regulation by kinases and mitochondrial ΔΨ. We will also focus on the heterogeneity of its expression in distinct mitochondrial populations and the pathophysiological implication of its excessive degradation. We will describe the ongoing debate on the stoichiometry of Na + to Ca 2+ transport, mediated by NCLX, and its physiological implication. We will focus on the major effects of mitochondrial Na + signaling by NCLX on mitochondrial metabolism in health; and finally, we will discuss the role NCLX plays in a wide range of health disorders, from heart failure and cancer to Parkinson and Alzheimer disease, making it a prime candidate for therapeutic targeting.
Keywords: Calcium; Mitochondria; Mitochondrial calcium signaling; NCLX; Sodium.
Copyright © 2020. Published by Elsevier Ltd.