A Pair of Transporters Controls Mitochondrial Zn Levels to Maintain Mitochondrial Homeostasis

Overview

Journal Protein Cell

Publisher Oxford University Press

Specialties Biochemistry
Cell Biology

Date 2021 Oct 23

PMID 34687432

Citations 15

Authors

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

Affiliations

Soon will be listed here.

Abstract

Zn 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 Zn 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 Zn. We demonstrate that SLC-30A9/ZnT9 is a mitochondrial Zn exporter. Loss of SLC-30A9 leads to mitochondrial Zn 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 Zn import. Loss of SLC-25A25 suppresses the abnormal mitochondrial Zn accumulation and defective mitochondrial structure and functions caused by loss of SLC-30A9. Moreover, we reveal that the endoplasmic reticulum contains the Zn pool from which mitochondrial Zn is imported. These findings establish the molecular basis for controlling the correct mitochondrial Zn levels for normal mitochondrial structure and functions.

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