A mutation in SLC30A9, a zinc transporter, causes an increased sensitivity to oxidative stress in the nematode Caenorhabditis elegans
A mutation in SLC30A9, a zinc transporter, causes an increased sensitivity to oxidative stress in the nematode Caenorhabditis elegans
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DOI：
10.1016/j.bbrc.2022.09.107
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发表时间：
2022-10-14
影响因子：
3.1
通讯作者：
Fujii, Michihiko
中科院分区：
文献类型：
--
作者：
En, Atsuki;Takanashi, Shuo;Fujii, Michihiko
氧气是有氧生物体所必需的，但会产生活性氧（ROS），这可能会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的调控，然而，人们对它们的关注并不多。为了确定这些基因，我们筛选突变体的敏感性改变氧化应激线虫线虫小杆线虫。我们分离了一个新的突变体，oxy-7（qa 5004），它在C.优雅的。oxy-7由于其增加的氧化应激而显示增加的ROS产生和减少的寿命。遗传分析显示，oxy-7在Y71H2AM.9中具有致病突变，Y71H2AM.9是SLC 30 A9的同源物，其编码线粒体中的锌转运蛋白。我们进一步表明，人SLC 30 A9的敲低也引起人细胞中ROS产生的增加。这些结果表明，线粒体锌稳态在ROS的调节中起重要作用。(c)2022爱思唯尔公司All rights reserved.
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.