自噬
细胞生物学
细胞内
氧化应激
线粒体
程序性细胞死亡
诱导剂
蛋白激酶A
生物
化学
激酶
生物化学
细胞凋亡
基因
作者
Yuki Takakura,Moeka Machida,Natsumi Terada,Yoshiki Katsumi,Shingo Kawamura,Kenta Horie,Mutsumi Miyauchi,Tatsuya Ishikawa,Nobuko Akiyama,Takao Seki,Takahisa Miyao,Mio Hayama,Rokuro Endo,Hiroto Ishii,Yuya Maruyama,Naoto Hagiwara,Tetsuya Kobayashi,Naoto Yamaguchi,Hiroyuki Takano,Taishin Akiyama,Noritaka Yamaguchi
标识
DOI:10.1101/2023.10.17.562644
摘要
ABSTRACT Autophagy is primarily activated by cellular stress, such as starvation or mitochondrial damage. However, stress-independent autophagy is activated by unknown mechanisms in several cell types, such as thymic epithelial cells (TECs). Here we report that the mitochondrial protein, C15ORF48, is a critical inducer of stress-independent autophagy. Mechanistically, C15ORF48 reduces the mitochondrial membrane potential and lowers intracellular ATP levels, thereby activating AMP-activated protein kinase and its downstream Unc-51-like kinase 1. Interestingly, C15ORF48 induction of autophagy upregulates intracellular glutathione levels, promoting cell survival by reducing oxidative stress. Mice deficient in C15orf48 showed a reduction in stress-independent autophagy in TECs, but not in typical starvation-induced autophagy in skeletal muscles. Moreover, C15orf48 −/– mice developed autoimmunity, which is consistent with the fact that the stress-independent autophagy in TECs is crucial for the thymic self-tolerance. These results suggest that C15ORF48 induces stress-independent autophagy, thereby regulating oxidative stress and self-tolerance.
科研通智能强力驱动
Strongly Powered by AbleSci AI