Journal article
ATG12 Conjugation to ATG3 Regulates Mitochondrial Homeostasis and Cell Death
Cell (Cambridge), Vol.142(4), pp.590-600
2010
DOI: 10.1016/j.cell.2010.07.018
PMCID: PMC2925044
PMID: 20723759
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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► The autophagy ubiquitin-like modifier ATG12 is conjugated to ATG3 ► ATG12-ATG3 complex does not affect starvation-induced autophagy ► ATG12-ATG3 restricts mitochondrial mass and promotes mitochondrial fusion ► Disrupting ATG12 conjugation to ATG3 renders cells resistant to mitochondrial cell death
Details
- Title: Subtitle
- ATG12 Conjugation to ATG3 Regulates Mitochondrial Homeostasis and Cell Death
- Creators
- Lilliana Radoshevich - Department of Pathology and Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA 94143, USALyndsay Murrow - Department of Pathology and Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA 94143, USANan Chen - Department of Pathology and Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA 94143, USAEstefania Fernandez - Department of Pathology and Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA 94143, USASrirupa Roy - Department of Pathology and Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA 94143, USAChristopher Fung - Department of Pathology and Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA 94143, USAJayanta Debnath - Department of Pathology and Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA 94143, USA
- Resource Type
- Journal article
- Publication Details
- Cell (Cambridge), Vol.142(4), pp.590-600
- Publisher
- Elsevier Inc
- DOI
- 10.1016/j.cell.2010.07.018
- PMID
- 20723759
- PMCID
- PMC2925044
- ISSN
- 0092-8674
- eISSN
- 1097-4172
- Language
- English
- Date published
- 2010
- Academic Unit
- Molecular Physiology and Biophysics; Microbiology and Immunology
- Record Identifier
- 9984025307502771
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