We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
Mitochondrial protein C15ORF48 is a stress-independent inducer of autophagy that regulates oxidative stress and autoimmunity.
- Authors
Takakura, Yuki; Machida, Moeka; Terada, Natsumi; Katsumi, Yuka; Kawamura, Seika; Horie, Kenta; Miyauchi, Maki; Ishikawa, Tatsuya; Akiyama, Nobuko; Seki, Takao; Miyao, Takahisa; Hayama, Mio; Endo, Rin; Ishii, Hiroto; Maruyama, Yuya; Hagiwara, Naho; Kobayashi, Tetsuya J.; Yamaguchi, Naoto; Takano, Hiroyuki; Akiyama, Taishin
- Abstract
Autophagy is primarily activated by cellular stress, such as starvation or mitochondrial damage. However, stress-independent autophagy is activated by unclear 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-dependent induction of autophagy upregulates intracellular glutathione levels, promoting cell survival by reducing oxidative stress. Mice deficient in C15orf48 show a reduction in stress-independent autophagy in TECs, but not in typical starvation-induced autophagy in skeletal muscles. Moreover, C15orf48–/– mice develop 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. Stress-independent autophagy is less understood than stress-induced autophagy and is important for thymic self-tolerance. Here the authors show that a mitochondrial protein C15ORF48 is important for stress-independent autophagy and alters glutathione metabolism and C15orf48 knockout mice develop autoimmunity and changes to thymic epithelial cells.
- Publication
Nature Communications, 2024, Vol 15, Issue 1, p1
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-024-45206-1