Cited by 1,001

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Discovery of Atg5/Atg7-independent alternative macroautophagy

Nishida, Yuya, Arakawa, Satoko, Fujitani, Kenji, Yamaguchi, Hirofumi, Mizuta, Takeshi, Kanaseki, Toku, Komatsu, Masaaki, Otsu, Kinya, Tsujimoto, Yoshihide, Shimizu, Shigeomi·2009·Nature

Abstract

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.

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Crossref · 10.1038/nature08455

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Research works printed but not linked: 21

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Metadata

Authors
Nishida, Y., Arakawa, S., Fujitani, K., Yamaguchi, H., Mizuta, T., Kanaseki, T., Komatsu, M., Otsu, K., Tsujimoto, Y., & Shimizu, S.
Venue
Nature
Published
2009-10-01
Volume
461
Issue
7264
Pages
654-658
ISSN
  • 0028-0836
  • 1476-4687
Cited by
1,001
References
7
Language
en

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