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Discovery of Atg5/Atg7-independent alternative macroautophagy
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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In addition to LC3, SQSTM1, or other receptors such as NBR1, can also be used as protein markers, at least in certain settings.
“In addition to LC3, SQSTM1, or other receptors such as NBR1, can also be used as protein markers, at least in certain settings [31,552].”
From Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition) 1 (2021) · cites this paper as [31]
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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
- Update notices
- correction (2016-01-20)
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