First Author | Radoshevich L | Year | 2010 |
Journal | Cell | Volume | 142 |
Issue | 4 | Pages | 590-600 |
PubMed ID | 20723759 | Mgi Jnum | J:164739 |
Mgi Id | MGI:4835103 | Doi | 10.1016/j.cell.2010.07.018 |
Citation | Radoshevich L, et al. (2010) ATG12 conjugation to ATG3 regulates mitochondrial homeostasis and cell death. Cell 142(4):590-600 |
abstractText | ATG12, an ubiquitin-like modifier required for macroautophagy, has a single known conjugation target, another autophagy regulator called ATG5. Here, we identify ATG3 as a substrate for ATG12 conjugation. ATG3 is the E2-like enzyme necessary for ATG8/LC3 lipidation during autophagy. ATG12-ATG3 complex formation requires ATG7 as the E1 enzyme and ATG3 autocatalytic activity as the E2, resulting in the covalent linkage of ATG12 onto a single lysine on ATG3. Surprisingly, disrupting ATG12 conjugation to ATG3 does not affect starvation-induced autophagy. Rather, the lack of ATG12-ATG3 complex formation produces an expansion in mitochondrial mass and inhibits cell death mediated by mitochondrial pathways. Overall, these results unveil a role for ATG12-ATG3 in mitochondrial homeostasis and implicate the ATG12 conjugation system in cellular functions distinct from the early steps of autophagosome formation. |