A pair of transporters controls mitochondrial Zn2+levels to maintain mitochondrial homeostasis

• 作者: 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
• 来源期刊: 蛋白质与细胞
• 年，卷（期）: 2022,（3）
• 所属期刊栏目: RESEARCH ARTICLES
• 页码范围: 180-202
• 页数: 23页
• 语种: 英文

摘要

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 mito-chondrial level of Zn2+.We demonstrate that SLC-30A9/ZnT9 is a mitochondrial Zn2+exporter.Loss of SLC-30A9 leads to mitochondrial Zn2+accumulation,which dam-ages 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 mito-chondrial structure and functions caused by loss of SLC-30A9.Moreover,we reveal that the endoplasmic reticulum contains the Zn2+pool from which mitochon-drial Zn2+is imported.These findings establish the molecular basis for controlling the correct mitochondrial Zn2+levels for normal mitochondrial structure and functions.