PNAS, 31 August, 2021, DOI：https://doi.org/10.1073/pnas.2023909118

SLC-30A9 is required for Zn²⁺ homeostasis, Zn²⁺ mobilization, and mitochondrial health

Huichao Deng, Xinhua Qiao, Ting Xie, Wenfeng Fu, Hang Li, Yanmei Zhao, Miaomiao Guo, Yaqian Feng, Ligong Chen, Yan Zhao, Long Miao, Chang Chen, Kang Shen, and Xiangming Wang

Abstract

The trace element zinc is essential for many aspects of physiology. The mitochondrion is a major Zn²⁺ store, and excessive mitochondrial Zn²⁺ is linked to neurodegeneration. How mitochondria maintain their Zn²⁺ homeostasis is unknown. Here, we find that the SLC-30A9 transporter localizes on mitochondria and is required for export of Zn²⁺ from mitochondria in both Caenorhabditis elegans and human cells. Loss of slc-30a9 leads to elevated Zn²⁺ levels in mitochondria, a severely swollen mitochondrial matrix in many tissues, compromised mitochondrial metabolic function, reductive stress, and induction of the mitochondrial stress response. SLC-30A9 is also essential for organismal fertility and sperm activation in C. elegans, during which Zn²⁺ exits from mitochondria and acts as an activation signal. In slc-30a9–deficient neurons, misshapen mitochondria show reduced distribution in axons and dendrites, providing a potential mechanism for the Birk–Landau–Perez cerebrorenal syndrome where an SLC30A9 mutation was found.

Article link：https://www.pnas.org/content/118/35/e2023909118