Graduate School of Nanobioscience, Yokohama City University, 22-2 Seto, Kanazawa-ku, Yokohama, 236-0027, Japan.
Graduate School of Nanobioscience, Yokohama City University, 22-2 Seto, Kanazawa-ku, Yokohama, 236-0027, Japan.
Biochem Biophys Res Commun. 2022 Dec 17;634:175-181. doi: 10.1016/j.bbrc.2022.09.107. Epub 2022 Oct 8.
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.
氧气是需氧生物所必需的，但会产生活性氧（ROS），这些 ROS 通过破坏细胞分子而导致细胞功能障碍。许多基因参与了 ROS 的调节；然而，人们并没有过多关注它们。为了鉴定这些基因，我们在秀丽隐杆线虫中筛选了对氧化应激敏感性改变的突变体。我们分离到一个新的突变体 oxy-7(qa5004)，它在 C. elegans 中对 ROS 的敏感性增加。oxy-7 由于氧化应激增加而表现出 ROS 产生增加和寿命缩短。遗传分析表明，oxy-7 在 Y71H2AM.9 中存在一个致病突变，该基因是 SLC30A9 的同源物，SLC30A9 编码线粒体中的锌转运体。我们进一步表明，敲低人 SLC30A9 也会导致人细胞中 ROS 的产生增加。这些结果表明线粒体锌稳态在 ROS 调节中起着重要作用。
