A pair of transporters controls mitochondrial Zn2+ levels to maintain mitochondrial homeostasis. Issue 3 (23rd October 2021)

• Record Type: Journal Article
• Authors: 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
• Is Part Of: Protein & cell. Volume 13:Issue 3(2022)
• Page Start: 180
• Page End: 202
• Publication Date: 2021-10-23
• Subjects: mitochondria -- Zn2+ transporter -- C. elegans -- ER-mitochondrial contact -- development; Proteins -- Periodicals; Cells -- Periodicals; Cytology -- Periodicals; 572.6
• DOI: 10.1007/s13238-021-00881-4
• Languages: English
• ISSNs: 1674-800X

Abstract

ABSTRACT: Zn 2+ 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 2+ 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 2+ . We demonstrate that SLC-30A9/ZnT9 is a mitochondrial Zn 2+ exporter. Loss of SLC-30A9 leads to mitochondrial Zn 2+ 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 2+ import. Loss of SLC-25A25 suppresses the abnormal mitochondrial Zn 2+ accumulation and defective mitochondrial structure and functions caused by loss of SLC-30A9. Moreover, we reveal that the endoplasmic reticulum contains the Zn 2+ pool from which mitochondrial Zn 2+ is imported. These findings establish the molecular basis for controlling the correct mitochondrial Zn 2+ levels for normal mitochondrial structure and functions.