| Title |
ATG12 Conjugation to ATG3 Regulates Mitochondrial Homeostasis and Cell Death
|
|---|---|
| Published in |
Cell, August 2010
|
| DOI | 10.1016/j.cell.2010.07.018 |
| Pubmed ID | |
| Authors |
Lilliana Radoshevich, Lyndsay Murrow, Nan Chen, Estefania Fernandez, Srirupa Roy, Christopher Fung, Jayanta Debnath |
| Abstract |
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. |
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Mendeley demographics
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United States | 6 | 2% |
| Germany | 5 | 2% |
| France | 2 | <1% |
| China | 2 | <1% |
| Trinidad and Tobago | 1 | <1% |
| Russia | 1 | <1% |
| Netherlands | 1 | <1% |
| Japan | 1 | <1% |
| United Kingdom | 1 | <1% |
| Other | 2 | <1% |
| Unknown | 266 | 92% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Ph. D. Student | 63 | 22% |
| Researcher | 62 | 22% |
| Student > Master | 31 | 11% |
| Professor > Associate Professor | 19 | 7% |
| Student > Bachelor | 17 | 6% |
| Other | 49 | 17% |
| Unknown | 47 | 16% |
| Readers by discipline | Count | As % |
|---|---|---|
| Agricultural and Biological Sciences | 124 | 43% |
| Biochemistry, Genetics and Molecular Biology | 67 | 23% |
| Medicine and Dentistry | 17 | 6% |
| Immunology and Microbiology | 7 | 2% |
| Pharmacology, Toxicology and Pharmaceutical Science | 4 | 1% |
| Other | 18 | 6% |
| Unknown | 51 | 18% |