Center for Translational Medicine, Lewis Katz School of Medicine at Temple University, Philadelphia, PA 19140, USA.
Cell Calcium. 2020 Dec;92:102288. doi: 10.1016/j.ceca.2020.102288. Epub 2020 Sep 11.
Calcium (Ca) is known to stimulate mitochondrial bioenergetics through the modulation of TCA cycle dehydrogenases and electron transport chain (ETC) complexes. This is hypothesized to be an essential pathway of energetic control to meet cellular ATP demand. While regulatory mechanisms of mitochondrial calcium uptake have been reported, it remains unknown if metabolite flux itself feedsback to regulate mitochondrial calcium (Ca) uptake. This hypothesis was recently tested by Nemani et al. (Sci. Signal. 2020) where the authors report that TCA cycle substrate flux regulates the mitochondrial calcium uniporter channel gatekeeper, mitochondrial calcium uptake 1 (MICU1), gene transcription in an early growth response protein 1 (EGR1) dependent fashion. They posit this is a regulatory feedback mechanism to control ionic homeostasis and mitochondrial bioenergetics with changing fuel availability. Here, we provide a historical overview of mitochondrial calcium exchange and comprehensive appraisal of these results in the context of recent literature and discuss possible regulatory pathways of Ca uptake and mitochondrial bioenergetics.
钙（Ca）被认为通过调节三羧酸（TCA）循环脱氢酶和电子传递链（ETC）复合物来刺激线粒体生物能学。这被假设为满足细胞 ATP 需求的能量控制的基本途径。虽然已经报道了线粒体钙摄取的调节机制，但尚不清楚代谢物通量本身是否会反馈调节线粒体钙（Ca）摄取。Nemani 等人最近检验了这一假设（《科学信号》，2020 年），作者报告说 TCA 循环底物通量以早期生长反应蛋白 1（EGR1）依赖的方式调节线粒体钙单向转运通道门控蛋白、线粒体钙摄取 1（MICU1）的基因转录。他们认为这是一种调节反馈机制，用于控制离子动态平衡和随燃料可用性变化的线粒体生物能学。在这里，我们提供了线粒体钙交换的历史概述，并根据最近的文献对这些结果进行了全面评估，并讨论了 Ca 摄取和线粒体生物能学的可能调节途径。
