1.A pair of transporters controls mitochondrial Zn2+ levels to maintain mitochondrial homeostasis.
Tengfei MA ; Liyuan ZHAO ; Jie ZHANG ; Ruofeng TANG ; Xin WANG ; Nan LIU ; Qian ZHANG ; Fengyang WANG ; Meijiao LI ; Qian SHAN ; Yang YANG ; Qiuyuan YIN ; Limei YANG ; Qiwen GAN ; Chonglin YANG
Protein & Cell 2022;13(3):180-202
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.
Animals
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Caenorhabditis elegans/metabolism*
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Cation Transport Proteins/genetics*
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Homeostasis
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Mitochondria/metabolism*
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Zinc/metabolism*
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