SLC-30A9 is required for Zn 2+ homeostasis, Zn 2+ mobilization, and mitochondrial health

Significance Zinc plays important roles in numerous cellular processes. Deficiency or excess of Zn2+ leads to many diseases. Zn2+ concentration at various cellular compartments is regulated. Imbalance of Zn2+ in mitochondria has been linked to neurodegeneration. However, little is known about how mitochondrial Zn2+ is regulated. We find that SLC-30A9 is required for Zn2+ export from mitochondria in bothCaenorhabditis elegans and human cells. Loss ofslc-30a9 leads to excessive Zn2+ 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.