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A pair of transporters controls mitochondrial Zn2+ levels to maintain mitochondrial homeostasis
Protein & Cell  (IF14.87),  Pub Date : 2021-10-23, DOI: 10.1007/s13238-021-00881-4
Ma, Tengfei, Zhao, Liyuan, Zhang, Jie, Tang, Ruofeng, Wang, Xin, Liu, Nan, Zhang, Qian, Wang, Fengyang, Li, Meijiao, Shan, Qian, Yang, Yang, Yin, Qiuyuan, Yang, Limei, Gan, Qiwen, Yang, Chonglin

Zn2+ is required for the activity of many mitochondrial proteins, which regulate mitochondrial dynamics, apoptosis and mitophagy. However, it is not understood how the proper mitochondrial Zn2+ level is achieved to maintain mitochondrial homeostasis. Using Caenorhabditis elegans, we reveal here that a pair of mitochondrion-localized transporters controls the mitochondrial level of Zn2+. We demonstrate that SLC-30A9/ZnT9 is a mitochondrial Zn2+ exporter. Loss of SLC-30A9 leads to mitochondrial Zn2+ accumulation, which damages mitochondria, impairs animal development and shortens the life span. We further identify SLC-25A25/SCaMC-2 as an important regulator of mitochondrial Zn2+ import. Loss of SLC-25A25 suppresses the abnormal mitochondrial Zn2+ accumulation and defective mitochondrial structure and functions caused by loss of SLC-30A9. Moreover, we reveal that the endoplasmic reticulum contains the Zn2+ pool from which mitochondrial Zn2+ is imported. These findings establish the molecular basis for controlling the correct mitochondrial Zn2+ levels for normal mitochondrial structure and functions.