| First Author | Sun L | Year | 2022 |
| Journal | Sci Adv | Volume | 8 |
| Issue | 31 | Pages | eabo0412 |
| PubMed ID | 35921421 | Mgi Jnum | J:343848 |
| Mgi Id | MGI:7332350 | Doi | 10.1126/sciadv.abo0412 |
| Citation | Sun L, et al. (2022) Deacetylation of ATG4B promotes autophagy initiation under starvation. Sci Adv 8(31):eabo0412 |
| abstractText | Eukaryotes initiate autophagy when facing environmental changes such as a lack of external nutrients. However, the mechanisms of autophagy initiation are still not fully elucidated. Here, we showed that deacetylation of ATG4B plays a key role in starvation-induced autophagy initiation. Specifically, we demonstrated that ATG4B is activated during starvation through deacetylation at K39 by the deacetylase SIRT2. Moreover, starvation triggers SIRT2 dephosphorylation and activation in a cyclin E/CDK2 suppression-dependent manner. Meanwhile, starvation down-regulates p300, leading to a decrease in ATG4B acetylation at K39. K39 deacetylation also enhances the interaction of ATG4B with pro-LC3, which promotes LC3-II formation. Furthermore, an in vivo experiment using Sirt2 knockout mice also confirmed that SIRT2-mediated ATG4B deacetylation at K39 promotes starvation-induced autophagy initiation. In summary, this study reveals an acetylation-dependent regulatory mechanism that controls the role of ATG4B in autophagy initiation in response to nutritional deficiency. |
