Spatial control of avidity regulates initiation and progression of selective autophagy

David M. Hollenstein, Mariya Licheva, Nicole Konradi, David Schweida, Hector Mancilla, Muriel Mari, Fulvio Reggiori and Claudine Kraft ()
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David M. Hollenstein: University of Vienna, Vienna BioCenter (VBC)
Mariya Licheva: University of Freiburg
Nicole Konradi: University of Freiburg
David Schweida: University of Vienna, Vienna BioCenter (VBC)
Hector Mancilla: University of Freiburg
Muriel Mari: University of Groningen, University Medical Center Groningen
Fulvio Reggiori: University of Groningen, University Medical Center Groningen
Claudine Kraft: University of Freiburg

Nature Communications, 2021, vol. 12, issue 1, 1-18

Abstract: Abstract Autophagosomes form at the endoplasmic reticulum in mammals, and between the vacuole and the endoplasmic reticulum in yeast. However, the roles of these sites and the mechanisms regulating autophagosome formation are incompletely understood. Vac8 is required for autophagy and recruits the Atg1 kinase complex to the vacuole. Here we show that Vac8 acts as a central hub to nucleate the phagophore assembly site at the vacuolar membrane during selective autophagy. Vac8 directly recruits the cargo complex via the Atg11 scaffold. In addition, Vac8 recruits the phosphatidylinositol 3-kinase complex independently of autophagy. Cargo-dependent clustering and Vac8-dependent sequestering of these early autophagy factors, along with local Atg1 activation, promote phagophore assembly site assembly at the vacuole. Importantly, ectopic Vac8 redirects autophagosome formation to the nuclear membrane, indicating that the vacuolar membrane is not specifically required. We propose that multiple avidity-driven interactions drive the initiation and progression of selective autophagy.

Date: 2021
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-27420-3

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DOI: 10.1038/s41467-021-27420-3

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