The dynamin Vps1 mediates Atg9 transport to the sites of autophagosome formation

Autor(en): Arlt, Henning 
Raman, Babu
Filali-Mouncef, Yasmina
Hu, Yan
Leytens, Alexandre
Hardenberg, Ralph
Guimaraes, Rodrigo
Kriegenburg, Franziska
Mari, Muriel
Smaczynska-de Rooij, Iwona I.
Ayscough, Kathryn R.
Ungermann, Christian 
Dengjel, Joern
Reggiori, Fulvio
Stichwörter: Biochemistry & Molecular Biology; EARLY STEPS; GOLGI; GTPASE; IN-VIVO; MEMBRANE FISSION; PROTEIN COMPLEX; REGULATES ATG9; SACCHAROMYCES-CEREVISIAE; VACUOLE; VESICLE FORMATION
Erscheinungsdatum: 2023
Herausgeber: ELSEVIER
Enthalten in: JOURNAL OF BIOLOGICAL CHEMISTRY
Band: 299
Ausgabe: 5
Zusammenfassung: 
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 com-plex and dynamin Vps1 mutants alter Atg9 subcellular distri-bution and severely impair the autophagic flux by affecting two separate autophagy steps. We provide evidence that Vps1 in-teracts 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 auto-phagy 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.
DOI: 10.1016/j.jbc.2023.104712

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