Uniporter公司
生物
细胞生物学
线粒体
细胞内
钙信号传导
线粒体膜转运蛋白
氧化磷酸化
磷酸化
生物化学
胞浆
线粒体内膜
酶
作者
Chen-Wei Tsai,Madison Rodriguez,Anna M. Van Keuren,Charles B Phillips,Hannah M. Shushunov,Jessica E. Lee,Anastacia M. Garcia,Amrut V. Ambardekar,Joseph C. Cleveland,Julie A. Reisz,Catherine Proenza,Kathryn C. Chatfield,Ming-Feng Tsai
出处
期刊:Molecular Cell
[Elsevier]
日期:2022-10-01
卷期号:82 (19): 3661-3676.e8
被引量:11
标识
DOI:10.1016/j.molcel.2022.09.006
摘要
Mitochondrial Ca2+ uptake, mediated by the mitochondrial Ca2+ uniporter, regulates oxidative phosphorylation, apoptosis, and intracellular Ca2+ signaling. Previous studies suggest that non-neuronal uniporters are exclusively regulated by a MICU1-MICU2 heterodimer. Here, we show that skeletal-muscle and kidney uniporters also complex with a MICU1-MICU1 homodimer and that human/mouse cardiac uniporters are largely devoid of MICUs. Cells employ protein-importation machineries to fine-tune the relative abundance of MICU1 homo- and heterodimers and utilize a conserved MICU intersubunit disulfide to protect properly assembled dimers from proteolysis by YME1L1. Using the MICU1 homodimer or removing MICU1 allows mitochondria to more readily take up Ca2+ so that cells can produce more ATP in response to intracellular Ca2+ transients. However, the trade-off is elevated ROS, impaired basal metabolism, and higher susceptibility to death. These results provide mechanistic insights into how tissues can manipulate mitochondrial Ca2+ uptake properties to support their unique physiological functions.
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