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Autophagosome biogenesis comes out of the black box

Abstract

Macroautophagic clearance of cytosolic materials entails the initiation, growth and closure of autophagosomes. Cargo triggers the assembly of a web of cargo receptors and core machinery. Autophagy-related protein 9 (ATG9) vesicles seed the growing autophagosomal membrane, which is supplied by de novo phospholipid synthesis, phospholipid transport via ATG2 proteins and lipid flipping by ATG9. Autophagosomes close via ESCRT complexes. Here, we review recent discoveries that illuminate the molecular mechanisms of autophagosome formation and discuss emerging questions in this rapidly developing field.

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Fig. 1: Overview of autophagosome formation.
Fig. 2: Autophagy initiation.
Fig. 3: Autophagosome growth.
Fig. 4: Autophagosome closure.

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Acknowledgements

This work was supported by HFSP (RGP0026/2017 to J.H.H.) and NIH R01 GM111730 (to J.H.H.).

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Correspondence to James H. Hurley.

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J.H.H. is a co-founder of Casma Therapeutics.

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Chang, C., Jensen, L.E. & Hurley, J.H. Autophagosome biogenesis comes out of the black box. Nat Cell Biol 23, 450–456 (2021). https://doi.org/10.1038/s41556-021-00669-y

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