相扑蛋白
粒体自噬
秀丽隐杆线虫
RNA干扰
生物
细胞生物学
基因敲除
线粒体
泛素
基因
遗传学
自噬
核糖核酸
细胞凋亡
作者
James W. Larrick,Jasmine W Larrick,Andrew R Mendelsohn
标识
DOI:10.1089/rej.2020.2406
摘要
SUMOylation, a conserved protein post-translational modification that performs multiple functions including regulation of nuclear transport and transcription, is implicated in numerous biological processes including aging. RNAi knockdown of the sole Small Ubiquitin-like MOdifier (SUMO) gene, smo-1, in Caenorhabditis elegans shortened lifespan, whereas overexpression in the intestine modestly increased lifespan. Smo-1 is required for mitochondrial fission in a tissue-specific manner. Fission, in turn, is needed for mitophagy to maintain mitochondrial homeostasis during aging. SUMOlyation affects DAuer Formation (DAF)-16, which can be directly SUMOylated, and SKN-1, the homolog of mammalian Nrf2. These regulators play key roles in maintaining mitochondrial homeostasis. However, given the modest effect of overexpressing smo-1 on lifespan enhancement and potential interference with other genes that can promote increased lifespan, caution is advised in the translation of this study based on C. elegans. Although inhibitors of SUMOlyation have been developed for cancer and activators also have been identified, broad-acting biochemical pathway modifiers such as SUMO are often suboptimal drug targets and may not be as promising for antiaging applications as they first appear.
科研通智能强力驱动
Strongly Powered by AbleSci AI