Department of Physiology and Cell Biology, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, 84105, Israel.
Department of Physiology and Cell Biology, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, 84105, Israel.
Cell Calcium. 2021 Mar;94:102345. doi: 10.1016/j.ceca.2020.102345. Epub 2021 Jan 2.
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.
线粒体是细胞 Ca2+信号的主要枢纽。MCU 的鉴定，即线粒体 Ca2+内流介质，以及线粒体 Ca2+外排体 NCLX，是该领域的重大突破。它们的鉴定为研究其生理功能和调节方式提供了新的分子工具和动物模型。在这里，我们将重点关注在线粒体 Na+/Ca2+信号中起双重作用的线粒体 Na+/Ca2+交换体 NCLX。我们将讨论激酶和线粒体ΔΨ对 NCLX 调节模式的最新进展。我们还将重点关注其在不同线粒体群体中的表达异质性及其过度降解的病理生理意义。我们将描述关于 NCLX 介导的 Na+/Ca2+转运的计量比及其生理意义的持续争论。我们将重点讨论 NCLX 通过线粒体 Na+信号对线粒体代谢的主要影响，以及它在从心力衰竭和癌症到帕金森病和阿尔茨海默病等广泛健康障碍中的作用，使其成为治疗靶点的主要候选者。
