Autophagy Reports (Dec 2023)

The yeast dynamin-like GTPase Vps1 mediates Atg9 transport to the phagophore assembly site in Saccharomyces cerevisiae

  • Yan Hu,
  • Fulvio Reggiori

DOI
https://doi.org/10.1080/27694127.2023.2247309
Journal volume & issue
Vol. 2, no. 1

Abstract

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Macroautophagy/autophagy is a degradative pathway that plays an important role in maintaining cellular homeostasis in eukaryotes. During autophagy, cisternal compartments called phagophores are generated to sequester intracellular components; these structures mature into autophagosomes, which deliver the cargo into lysosomes/vacuoles for degradation. Numerous autophagy-related (Atg) proteins are part of the core machinery that mediates autophagosome biogenesis. Atg9, a lipid scramblase and the only multispanning transmembrane protein among the core Atg machinery, traffics between cytoplasmic reservoirs and the phagophore assembly site (PAS) to provide membranes, recruit other Atg proteins and rearrange lipids on the phagophore membrane. However, the factors mediating Atg9 trafficking remain to be fully understood. In our recent study, we found that the yeast dynamin-like GTPase Vps1 (vacuolar protein sorting 1) is involved in autophagy and is important for Atg9 transport to the PAS. Moreover, we showed that Vps1 function in autophagy requires its GTPase and oligomerization activities. Interestingly, specific mutations in DNM2 (dynamin 2), one of the human homologs of Vps1 that have been linked with specific human diseases such as microcytic anemia and Charcot-Marie-Tooth, also impairs Atg9 transport to the PAS, suggesting that a defect in autophagy may underlay the pathophysiology of these severe human pathologies. Abbreviations Ape1, aminopeptidase I; APEX2, ascorbate peroxidase 2; Atg, autophagy-related; Cvt, cytoplasm-to-vacuole targeting; Dnm1, dynamin-related 1; DNM2, dynamin 2; PAS, phagophore assembly site; TAKA, transport of Atg9 after knocking out ATG1; Vps1, vacuolar protein sorting 1.

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