Tang Dong, Guan Wenbin, Yang Xiaodi, Li Zhongqin, Zhao Wei, Liu Xinguang
Guangdong Provincial Key Laboratory of Medical Immunology and Molecular Diagnostics, Institute of Aging Research, Guangdong Medical University, Dongguan 523808, China.
School of Medical Technology, Guangdong Medical University, Dongguan 523808, China.
Biomolecules. 2025 Feb 12;15(2):271. doi: 10.3390/biom15020271.
Yeast was initially identified as a homolog of human TIMM8A/DDP1, which is associated with human deafness-dystonia syndrome. Tim8p is located in the mitochondrial intermembrane space and forms a hetero-oligomeric complex with Tim13p to facilitate protein transport through the TIM22 translocation system. Previous research has indicated that is not essential for yeast survival but does affect the import of Tim23p in the absence of the Tim8-Tim13 complex. Previous research on has focused mainly on its involvement in the mitochondrial protein transport pathway, and the precise biological function of remains incompletely understood. In this study, we provide the first report that yeast is associated with the endoplasmic reticulum (ER) stress response and chronological senescence. We found that deletion of leads to both oxidative stress and ER stress in yeast cells while increasing resistance to the ER stress inducer tunicamycin (TM), which is accompanied by an enhanced basic unfolded protein response (UPR). More importantly, deficiency can lead to a shortened chronological lifespan (CLS) but does not affect the replicative lifespan (RLS). Moreover, we found that improving the antioxidant capacity further increased TM resistance in the strain. Importantly, we provide evidence that the knockdown of TIMM8A in ARPE-19 human retinal pigment epithelium cells can also induce ER stress, suggesting the potential function of the gene in ER stress is conserved from budding yeast to higher eukaryotes. In summary, these results suggest novel roles for in maintaining ER homeostasis and CLS maintenance.
酵母最初被鉴定为人类TIMM8A/DDP1的同源物，后者与人类耳聋 - 肌张力障碍综合征相关。Tim8p位于线粒体内膜间隙，与Tim13p形成异源寡聚复合物，以促进蛋白质通过TIM22易位系统的转运。先前的研究表明，[此处原文缺失相关蛋白名称]对酵母存活并非必需，但在缺乏Tim8 - Tim13复合物的情况下确实会影响Tim23p的导入。先前对[此处原文缺失相关蛋白名称]的研究主要集中在其参与线粒体蛋白质转运途径，而其确切的生物学功能仍未完全了解。在本研究中，我们首次报道酵母[此处原文缺失相关蛋白名称]与内质网（ER）应激反应和时序衰老有关。我们发现缺失[此处原文缺失相关蛋白名称]会导致酵母细胞出现氧化应激和内质网应激，同时增加对内质网应激诱导剂衣霉素（TM）的抗性，这伴随着增强的基础未折叠蛋白反应（UPR）。更重要的是，[此处原文缺失相关蛋白名称]缺陷会导致时序寿命（CLS）缩短，但不影响复制寿命（RLS）。此外，我们发现提高抗氧化能力可进一步增加[此处原文缺失相关蛋白名称]缺陷菌株对TM的抗性。重要的是，我们提供的证据表明，在ARPE - 19人视网膜色素上皮细胞中敲低TIMM8A也可诱导内质网应激，这表明[此处原文缺失相关蛋白名称]基因在内质网应激中的潜在功能从芽殖酵母到高等真核生物是保守的。总之，这些结果表明[此处原文缺失相关蛋白名称]在维持内质网稳态和时序寿命维持中具有新作用。
