SLC-30A9 is required for Zn2+ homeostasis, Zn2+ mobilization, and mitochondrial health.
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.
['Deng|Huichao|H|0000-0002-1758-1820', 'Qiao|Xinhua|X|', 'Xie|Ting|T|', 'Fu|Wenfeng|W|0000-0003-2912-6443', 'Li|Hang|H|', 'Zhao|Yanmei|Y|0000-0002-3294-6971', 'Guo|Miaomiao|M|', 'Feng|Yaqian|Y|', 'Chen|Ligong|L|', 'Zhao|Yan|Y|', 'Miao|Long|L|0000-0002-0562-6681', 'Chen|Chang|C|', 'Shen|Kang|K|', 'Wang|Xiangming|X|0000-0002-5111-0512']
SLC-30A9 mitochondria Birk–Landau–Perez cerebrorenal syndrome Zn2+ transporters