ATG12 conjugation to ATG3 regulates mitochondrial homeostasis and cell death (Cell, 2010, 142:590-600)

報告日期: 2011/05/03
報告時間: 17:10/18:00
報告學生: 蕭綾儀 (英文報告)
講評老師: 徐麗君
附件下載:

Full Text: http://basicmed.med.ncku.edu.tw/admin/up_img/0503-3.pdf

ATG12 Conjugation to ATG3 Regulates Mitochondrial Homeostasis and Cell Death
Cell 142: 590–600(2010)
 
Commentator:Li-Jin Hsu, PhD
Speaker: Ling-Yi Xiao
Date: 2011/ 05/ 03
Classroom602
 
Ubiquitin-like proteins (UBLs) is a family of small proteins related to ubiquitin. Proteins such as Sumo, Atg8 or Atg12 belong to this family. Autophagic progression requires UBL conjugation. Unlike other UBLs, Atg5 was the only substrate reported for Atg12. In this paper, the authors demonstrated that Atg12 conjugated to other substrate beside Atg5. Moreover, this complex regulates mitochondrial homeostasis and mitochondria mediated cell death. First, they found that other proteins may also conjugate to Atg12 and one of them was identified as Atg3. Second, the authors discovered that lysine243 on Atg3 was important for the formation of Atg12-Atg3 complex. Then, Atg3 served as self-acting E2 enzyme and autocatalyzed the conjugation of Atg12-Atg3 complex. Although it was known that Atg3 was involved in the lipidation of LC3 and formation of autophagosome. However, the Atg12-Atg3 complex was found not to regulate autophagy. Third, they observed that disrupting Atg12-Atg3 conjugation stimulated the increase of mitochondrial mass and mitochondrial fragmentation. Finally, the results showed that Atg12-Atg3 complex affected mitochondria-mediated cell death. In summary, Atg3 was found to be a substrate of Atg12 in addition to Atg5; while Atg12 regulates not only autophagy but also mitochondrial homeostasis and cell death induced by mitochondria.
 
References
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