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The dynamin Vps1 mediates Atg9 transport to the sites of autophagosome formation.
- Source :
-
The Journal of biological chemistry [J Biol Chem] 2023 May; Vol. 299 (5), pp. 104712. Date of Electronic Publication: 2023 Apr 14. - Publication Year :
- 2023
-
Abstract
- Autophagy is a key process in eukaryotes to maintain cellular homeostasis by delivering cellular components to lysosomes/vacuoles for degradation and reuse of the resulting metabolites. Membrane rearrangements and trafficking events are mediated by the core machinery of autophagy-related (Atg) proteins, which carry out a variety of functions. How Atg9, a lipid scramblase and the only conserved transmembrane protein within this core Atg machinery, is trafficked during autophagy remained largely unclear. Here, we addressed this question in yeast Saccharomyces cerevisiae and found that retromer complex and dynamin Vps1 mutants alter Atg9 subcellular distribution and severely impair the autophagic flux by affecting two separate autophagy steps. We provide evidence that Vps1 interacts with Atg9 at Atg9 reservoirs. In the absence of Vps1, Atg9 fails to reach the sites of autophagosome formation, and this results in an autophagy defect. The function of Vps1 in autophagy requires its GTPase activity. Moreover, Vps1 point mutants associated with human diseases such as microcytic anemia and Charcot-Marie-Tooth are unable to sustain autophagy and affect Atg9 trafficking. Together, our data provide novel insights on the role of dynamins in Atg9 trafficking and suggest that a defect in this autophagy step could contribute to severe human pathologies.<br />Competing Interests: Conflict of interest The authors declare no conflicts of interest in regard to this article.<br /> (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)
- Subjects :
- Humans
Saccharomyces cerevisiae genetics
Saccharomyces cerevisiae metabolism
Dynamins metabolism
Vacuoles metabolism
Autophagy
Autophagy-Related Proteins genetics
Autophagy-Related Proteins metabolism
Protein Transport
GTP-Binding Proteins metabolism
Vesicular Transport Proteins genetics
Vesicular Transport Proteins metabolism
Membrane Proteins metabolism
Autophagosomes metabolism
Saccharomyces cerevisiae Proteins genetics
Saccharomyces cerevisiae Proteins metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1083-351X
- Volume :
- 299
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- The Journal of biological chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 37060997
- Full Text :
- https://doi.org/10.1016/j.jbc.2023.104712