ATG12 Conjugation to ATG3 Regulates Mitochondrial Homeostasis and Cell Death
| Autor: | Christopher Fung, Jayanta Debnath, Estefania Fernandez, Srirupa Roy, Lilliana Radoshevich, Nan Chen, Lyndsay M. Murrow |
|---|---|
| Rok vydání: | 2010 |
| Předmět: |
Programmed cell death
PROTEINS ATG8 Molecular Sequence Data ATG5 Autophagy-Related Proteins Ubiquitin-conjugating enzyme Mitochondrion Biology Autophagy-Related Protein 7 Article General Biochemistry Genetics and Molecular Biology Autophagy-Related Protein 5 Cell Line ATG12 03 medical and health sciences Cell Line Tumor Phagosomes Autophagy Humans Amino Acid Sequence 030304 developmental biology 0303 health sciences Cell Death Biochemistry Genetics and Molecular Biology(all) 030302 biochemistry & molecular biology Fibroblasts Embryo Mammalian Mitochondria Cell biology Ubiquitin-Conjugating Enzymes Small Ubiquitin-Related Modifier Proteins CELLBIO Microtubule-Associated Proteins Autophagy-Related Protein 12 HeLa Cells |
| Zdroj: | Cell. 142:590-600 |
| ISSN: | 0092-8674 |
| DOI: | 10.1016/j.cell.2010.07.018 |
| Popis: | SummaryATG12, 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. |
| Databáze: | OpenAIRE |
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