A pair of transporters controls mitochondrial Zn2+ levels to maintain mitochondrial homeostasis.
10.1007/s13238-021-00881-4
- Author:
Tengfei MA
1
;
Liyuan ZHAO
1
;
Jie ZHANG
2
;
Ruofeng TANG
1
;
Xin WANG
1
;
Nan LIU
1
;
Qian ZHANG
1
;
Fengyang WANG
1
;
Meijiao LI
1
;
Qian SHAN
1
;
Yang YANG
1
;
Qiuyuan YIN
1
;
Limei YANG
1
;
Qiwen GAN
1
;
Chonglin YANG
3
Author Information
1. State Key Laboratory of Conservation and Utilization of Bio-resources in Yunnan and Center for Life Sciences, School of Life Sciences, Yunnan University, Kunming, 650091, China.
2. State Key Laboratory of Conservation and Utilization of Bio-resources in Yunnan and Center for Life Sciences, School of Life Sciences, Yunnan University, Kunming, 650091, China. zhangjiea@ynu.edu.cn.
3. State Key Laboratory of Conservation and Utilization of Bio-resources in Yunnan and Center for Life Sciences, School of Life Sciences, Yunnan University, Kunming, 650091, China. clyang@ynu.edu.cn.
- Publication Type:Research Support, Non-U.S. Gov't
- Keywords:
C. elegans;
ER-mitochondrial contact;
Zn2+ transporter;
development;
mitochondria
- MeSH:
Animals;
Caenorhabditis elegans/metabolism*;
Cation Transport Proteins/genetics*;
Homeostasis;
Mitochondria/metabolism*;
Zinc/metabolism*
- From:
Protein & Cell
2022;13(3):180-202
- CountryChina
- Language:English
-
Abstract:
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.
