Conserved role of ENDOG in promoting autophagy
| Autor: | Jianshuang Li, Qinghua Zhou, Wenjun Wang |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
DNA damage ENDOG Apoptosis Mitochondrion Cell Line Gene Knockout Techniques Mice 03 medical and health sciences Endonuclease Tuberous Sclerosis Complex 2 Protein Autophagy Animals Humans Phosphorylation Caenorhabditis elegans Molecular Biology GSK3B PI3K/AKT/mTOR pathway Mice Knockout Endodeoxyribonucleases 030102 biochemistry & molecular biology biology TOR Serine-Threonine Kinases Hep G2 Cells Cell Biology Class III Phosphatidylinositol 3-Kinases Autophagic Punctum Mitochondria Cell biology 030104 developmental biology 14-3-3 Proteins Liver biology.protein Drosophila Transcriptome DNA Damage Signal Transduction |
| Zdroj: | Autophagy |
| ISSN: | 1554-8635 1554-8627 |
| Popis: | Endonuclease G (ENDOG), a mitochondrial nuclease, is known to participate in many cellular processes, including apoptosis and paternal mitochondrial elimination, while its role in autophagy remains unclear. Here, we report that ENDOG released from mitochondria promotes autophagy during starvation, which we find to be evolutionally conserved across species by performing experiments in human cell lines, mice, Drosophila and C. elegans. Under starvation, Glycogen synthase kinase 3 beta-mediated phosphorylation of ENDOG at Thr-128 and Ser-288 enhances its interaction with 14-3-3γ, which leads to the release of Tuberin (TSC2) and Phosphatidylinositol 3-kinase catalytic subunit type 3 (Vps34) from 14-3-3γ, followed by mTOR pathway suppression and autophagy initiation. Alternatively, ENDOG activates DNA damage response and triggers autophagy through its endonuclease activity. Our results demonstrate that ENDOG is a crucial regulator of autophagy, manifested by phosphorylation-mediated interaction with 14-3-3γ, and its endonuclease activity-mediated DNA damage response. |
| Databáze: | OpenAIRE |
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