Guangdong Provincial Key Laboratory of Medical Molecular Diagnostics, Institute of Aging Research, Guangdong Medical University, Dongguan, 523808, China.
School of Medical Technology, Guangdong Medical University, Dongguan, China.
Antonie Van Leeuwenhoek. 2023 Aug;116(8):773-789. doi: 10.1007/s10482-023-01847-8. Epub 2023 May 24.
UPS1/YLR193C of Saccharomyces cerevisiae (S. cerevisiae) encodes a mitochondrial intermembrane space protein. A previous study found that Ups1p is needed for normal mitochondrial morphology and that UPS1 deficiency disrupts the intramitochondrial transport of phosphatidic acid in yeast cells and leads to an altered unfolded protein response and mTORC1 signaling activation. In this paper, we first provide evidence showing that the UPS1 gene is involved in the UVC-induced DNA damage response and aging. We show that UPS1 deficiency leads to sensitivity to ultraviolet C (UVC) radiation and that this effect is accompanied by elevated DNA damage, increased intracellular ROS levels, abnormal mitochondrial respiratory function, an increased early apoptosis rate, and shortened replicative lifespan and chronological lifespan. Moreover, we show that overexpression of the DNA damage-induced checkpoint gene RAD9 effectively eliminates the senescence-related defects observed in the UPS1-deficient strain. Collectively, these results suggest a novel role for UPS1 in the UVC-induced DNA damage response and aging.
酿酒酵母（Saccharomyces cerevisiae）的 UPS1/YLR193C 编码一种线粒体膜间空间蛋白。先前的研究发现，Ups1p 对于正常的线粒体形态是必需的，并且 UPS1 缺乏会破坏酵母细胞中线粒体中磷酸脂酸的内部转运，导致未折叠蛋白反应和 mTORC1 信号转导的激活改变。在本文中，我们首先提供证据表明 UPS1 基因参与 UVC 诱导的 DNA 损伤反应和衰老。我们表明 UPS1 缺乏会导致对紫外线 C（UVC）辐射的敏感性，并且这种效应伴随着 DNA 损伤增加、细胞内 ROS 水平升高、线粒体呼吸功能异常、早期凋亡率增加以及复制寿命和时序寿命缩短。此外，我们表明，DNA 损伤诱导的检查点基因 RAD9 的过表达可有效消除在 UPS1 缺陷型菌株中观察到的衰老相关缺陷。综上所述，这些结果表明 UPS1 在 UVC 诱导的 DNA 损伤反应和衰老中发挥了新的作用。
