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Acetylated microtubules are required for fusion of autophagosomes with lysosomes
Abstract
Background: Autophagy is a dynamic process during which isolation membranes package substrates to form autophagosomes that are fused with lysosomes to form autolysosomes for degradation. Although it is agreed that the LC3II-associated mature autophagosomes move along microtubular tracks, it is still in dispute if the conversion of LC3I to LC3II before autophagosomes are fully mature and subsequent fusion of mature autophagosomes with lysosomes require microtubules. Results: We use biochemical markers of autophagy and a collection of microtubule interfering reagents to test the question. Results show that interruption of microtubules with either microtubule stabilizing paclitaxel or destabilizing nocodazole similarly impairs the conversion of LC3I to LC3II, but does not block the degradation of LC3II-associated autophagosomes. Acetylation of microtubules renders them resistant to nocodazole treatment. Treatment with vinblastine that causes depolymerization of both non-acetylated and acetylated microtubules results in impairment of both LC3I-LC3II conversion and LC3II-associated autophagosome fusion with lysosomes. Conclusions: Acetylated microtubules are required for fusion of autophagosomes with lysosomes to form autolysosomes.
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“note that chloroquine blocks autophagy predominantly by inhibiting autophagosome-lysosome fusion [304]”
From Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition) 1 (2021) · cites this paper as [304]
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LC3, a mammalian homologue of yeast Apg8p, is localized in autophagosome membranes after processing.
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“The LC3 precursor is truncated to LC3I then conjugated with phosphatidylethanolamine to membrane-associated LC3II mediated by the ATG5-ATG12 conjugate [4,5].”
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Sorted by citations
Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition).
Klionsky, D. J., Abdelmohsen, K., Abe, A., Abedin, M. J., Abeliovich, H., Acevedo Arozena, A., Adachi, H., Adams, C. M., Adams, P. D., Adeli, K., et al. (2016) · Autophagy · doi:10.1080/15548627.2015.1100356 · Cited by 5,894
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Metadata
- Authors
- Xie, R., Nguyen, S., McKeehan, W. L., & Liu, L.
- Venue
- BMC Cell Biology
- Published
- 2010-11-22
- Volume
- 11
- Issue
- 1
- ISSN
- 1471-2121
- PMC
- PMC2995476
- Cited by
- 195
- References
- 11
- Language
- en
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