Guangdong Provincial Key Laboratory of Medical Molecular Diagnostics, Institute of Aging Research, Guangdong Medical University, Dongguan, 523808, China.
Institute of Biochemistry and Molecular Biology, Guangdong Medical University, Dongguan, 523808, China.
Biogerontology. 2021 Oct;22(5):547-563. doi: 10.1007/s10522-021-09935-w. Epub 2021 Sep 15.
YPK9/YOR291W of Saccharomyces cerevisiae encodes a vacuolar membrane protein. Previous research has suggested that Ypk9p is similar to the yeast P5-type ATPase Spf1p and that it plays a role in the sequestration of heavy metals. In addition, bioinformatics analysis has suggested that Ypk9p is a homolog of human ATP13A2, which encodes a protein of the subfamily of P5 ATPases. However, no specific function of Ypk9p has been described to date. In this study, we found, for the first time, that YPK9 is involved in the oxidative stress response and modulation of the replicative lifespan (RLS). We found that YPK9 deficiency confers sensitivity to the oxidative stress inducer hydrogen peroxide accompanied by increased intracellular ROS levels, decreased mitochondrial membrane potential, abnormal mitochondrial function, and increased incidence of early apoptosis in budding yeast. More importantly, YPK9 deficiency can lead to a shortened RLS. In addition, we found that overexpression of the catalase-encoding gene CTA1 can reverse the phenotypic abnormalities of the ypk9Δ yeast strain. Collectively, these findings highlight the involvement of Ypk9p in the oxidative stress response and modulation of RLS.
酿酒酵母的 YPK9/YOR291W 编码一种液泡膜蛋白。先前的研究表明，Ypk9p 类似于酵母 P5 型 ATP 酶 Spf1p，在重金属的隔离中发挥作用。此外，生物信息学分析表明 Ypk9p 是人类 ATP13A2 的同源物，后者编码 P5 ATP 酶亚家族的一种蛋白质。然而，迄今为止尚未描述 Ypk9p 的具体功能。在这项研究中，我们首次发现 YPK9 参与氧化应激反应和复制寿命（RLS）的调节。我们发现 YPK9 缺失使酵母对氧化应激诱导剂过氧化氢敏感，同时伴随着细胞内 ROS 水平升高、线粒体膜电位降低、线粒体功能异常以及早期凋亡的发生率增加。更重要的是，YPK9 缺失会导致 RLS 缩短。此外，我们发现过表达编码过氧化氢酶的基因 CTA1 可以逆转 ypk9Δ 酵母菌株的表型异常。总之，这些发现强调了 Ypk9p 在氧化应激反应和 RLS 调节中的作用。
