A mutation in SLC30A9, a zinc transporter, causes an increased sensitivity to oxidative stress in the nematode Caenorhabditis elegans

Oxygen is essential for aerobic organisms, but generates reactive oxygen species (ROS), which can cause cellular dysfunction by damaging cellular molecules. Many genes are involved in the regulation of ROS; however, much attention has not focused on them. To identify these genes, we screened for mutants with an altered sensitivity to oxidative stress in the nematode Caenorhabditis elegans. We isolated a novel mutant, oxy-7(qa5004) which showed an increased sensitivity to ROS in C. elegans. oxy-7 showed increased production of ROS and decreased longevity due to its increased oxidative stress. Genetic analysis revealed that oxy-7 has a causative mutation in Y71H2AM.9, a homologue of SLC30A9 which encodes a zinc transporter in mitochondria. We further showed that knockdown of human SLC30A9 caused increased ROS production in human cells as well. These results suggested an important role of mitochondrial zinc homeostasis in the regulation of ROS.(c) 2022 Elsevier Inc. All rights reserved.

Automated summary

This study identified a mutant oxy-7 in the nematode Caenorhabditis elegans that showed increased sensitivity to reactive oxygen species (ROS) due to a causative mutation in the gene Y71H2AM.9. Knockdown of the human homolog SLC30A9 also resulted in increased ROS production in human cells.