Reference - Detail
| RRC ID | 65366 |
|---|---|
| Author | Wang W, Li J, Tan J, Wang M, Yang J, Zhang ZM, Li C, Basnakian AG, Tang HW, Perrimon N, Zhou Q. |
| Title | Endonuclease G promotes autophagy by suppressing mTOR signaling and activating the DNA damage response. |
| Journal | Nat Commun |
| Abstract |
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. |
| Volume | 12(1) |
| Pages | 476 |
| Published | 2021-1-20 |
| DOI | 10.1038/s41467-020-20780-2 |
| PII | 10.1038/s41467-020-20780-2 |
| PMID | 33473107 |
| PMC | PMC7817833 |
| MeSH | 14-3-3 Proteins / metabolism Animals Apoptosis Autophagy / physiology* Caenorhabditis elegans Cell Line Class III Phosphatidylinositol 3-Kinases / metabolism DNA Damage / physiology* Drosophila Endodeoxyribonucleases / genetics* Endodeoxyribonucleases / metabolism* Gene Knockout Techniques Hep G2 Cells Humans Liver / metabolism Liver / pathology Mice Mice, Knockout Mitochondria / metabolism Phosphorylation Signal Transduction / physiology* TOR Serine-Threonine Kinases / metabolism* Transcriptome Tuberous Sclerosis Complex 2 Protein / metabolism |
| Altmetric score |
オルトメトリクス指標項目
|
| The most frequently cited source | X(Twitter) |
| Total number of mentions | 6 |
| Altmetric score changes over past 6months | 0.0 |
| Resource | |
| C.elegans | tm3222 |