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<p>Autophagosome biogenesis depends on the accurate delivery of membrane lipids to the pre-autophagosomal structure. Golgi/endosome-derived Atg9 vesicles provide the membrane seed for this process, but how they are trafficked through the cytoplasm while avoiding inappropriate fusion remains unclear. Here we show that in <i>Saccharomyces cerevisiae</i>, the soluble Atg9-interacting protein Atg23 remains associated with Atg9 vesicles after their biogenesis. This association shields Atg9 vesicles from aberrant SNARE-dependent fusion as they diffuse through the cytoplasm en route to the autophagosome formation site. We further show that upon vesicle arrival at the site, Atg9 phosphorylation by the autophagy initiation kinase Atg1 releases Atg23, facilitating recruitment of the downstream factor Atg2, a lipid transfer protein for membrane expansion. Together, these findings reveal an Atg1-dependent phosphorylation switch that regulates Atg9 vesicle dynamics during autophagosome biogenesis.</p>

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Atg23 prevents aberrant fusion of Atg9 vesicles during delivery to autophagosome formation sites

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年7月20日

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  • Takumi Kimura,
  • Takayuki Shima,
  • Tetsuya Kotani,
  • Hitoshi Nakatogawa

摘要

Autophagosome biogenesis depends on the accurate delivery of membrane lipids to the pre-autophagosomal structure. Golgi/endosome-derived Atg9 vesicles provide the membrane seed for this process, but how they are trafficked through the cytoplasm while avoiding inappropriate fusion remains unclear. Here we show that in Saccharomyces cerevisiae, the soluble Atg9-interacting protein Atg23 remains associated with Atg9 vesicles after their biogenesis. This association shields Atg9 vesicles from aberrant SNARE-dependent fusion as they diffuse through the cytoplasm en route to the autophagosome formation site. We further show that upon vesicle arrival at the site, Atg9 phosphorylation by the autophagy initiation kinase Atg1 releases Atg23, facilitating recruitment of the downstream factor Atg2, a lipid transfer protein for membrane expansion. Together, these findings reveal an Atg1-dependent phosphorylation switch that regulates Atg9 vesicle dynamics during autophagosome biogenesis.