SLC-30A9 is required for Zn

The trace element zinc is essential for many aspects of physiology. The mitochondrion is a major Zn(2+) store, and excessive mitochondrial Zn(2+) is linked to neurodegeneration. How mitochondria maintain their Zn(2+) homeostasis is unknown. Here, we find that the SLC-30A9 transporter localizes on mitochondria and is required for export of Zn(2+) from mitochondria in both Caenorhabditis elegans and human cells. Loss of slc-30a9 leads to elevated Zn(2+) 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 Zn(2+) 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.