SLC-30A9 is required for Zn <sup>2+</sup> homeostasis, Zn <sup>2+</sup> 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, Xiangming Wang
Abstract
Significance Zinc plays important roles in numerous cellular processes. Deficiency or excess of Zn 2+ leads to many diseases. Zn 2+ concentration at various cellular compartments is regulated. Imbalance of Zn 2+ in mitochondria has been linked to neurodegeneration. However, little is known about how mitochondrial Zn 2+ is regulated. We find that SLC-30A9 is required for Zn 2+ export from mitochondria in both Caenorhabditis elegans and human cells. Loss of slc-30a9 leads to excessive Zn 2+ accumulation in mitochondria, severe mitochondrial swelling, 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 neurons, slc-30a9 mutations cause dramatically reduced mitochondria in neurites, providing a potential mechanism for the Birk–Landau–Perez cerebrorenal syndrome.