Publication Date:
2009-10-02
Description:
Macroautophagy is a process that leads to the bulk degradation of subcellular constituents by producing autophagosomes/autolysosomes. It is believed that Atg5 (ref. 4) and Atg7 (ref. 5) are essential genes for mammalian macroautophagy. Here we show, however, that mouse cells lacking Atg5 or Atg7 can still form autophagosomes/autolysosomes and perform autophagy-mediated protein degradation when subjected to certain stressors. Although lipidation of the microtubule-associated protein light chain 3 (LC3, also known as Map1lc3a) to form LC3-II is generally considered to be a good indicator of macroautophagy, it did not occur during the Atg5/Atg7-independent alternative process of macroautophagy. We also found that this alternative process of macroautophagy was regulated by several autophagic proteins, including Unc-51-like kinase 1 (Ulk1) and beclin 1. Unlike conventional macroautophagy, autophagosomes seemed to be generated in a Rab9-dependent manner by the fusion of isolation membranes with vesicles derived from the trans-Golgi and late endosomes. In vivo, Atg5-independent alternative macroautophagy was detected in several embryonic tissues. It also had a function in clearing mitochondria during erythroid maturation. These results indicate that mammalian macroautophagy can occur through at least two different pathways: an Atg5/Atg7-dependent conventional pathway and an Atg5/Atg7-independent alternative pathway.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Nishida, Yuya -- Arakawa, Satoko -- Fujitani, Kenji -- Yamaguchi, Hirofumi -- Mizuta, Takeshi -- Kanaseki, Toku -- Komatsu, Masaaki -- Otsu, Kinya -- Tsujimoto, Yoshihide -- Shimizu, Shigeomi -- England -- Nature. 2009 Oct 1;461(7264):654-8. doi: 10.1038/nature08455.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pathological Cell Biology, Medical Research Institute, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19794493" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
Apoptosis Regulatory Proteins/metabolism
;
Autophagy/drug effects/*physiology
;
Etoposide/pharmacology
;
Fibroblasts/cytology/drug effects/metabolism
;
Food Deprivation
;
Mice
;
Mice, Knockout
;
Microtubule-Associated Proteins/*deficiency/genetics/metabolism
;
Phagosomes/drug effects/metabolism
;
Phosphatidylinositol 3-Kinases/metabolism
;
Protein-Serine-Threonine Kinases/metabolism
;
rab GTP-Binding Proteins/metabolism
Print ISSN:
0028-0836
Electronic ISSN:
1476-4687
Topics:
Biology
,
Chemistry and Pharmacology
,
Medicine
,
Natural Sciences in General
,
Physics
Permalink
