Autophagosome biogenesis comes out of the black box.

Chunmei Chang,James H Hurley,Liv E Jensen

doi:10.1038/s41556-021-00669-y

Chunmei Chang, James H Hurley + Show 1 more

Open Access

https://doi.org/10.1038/s41556-021-00669-y

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Journal: Nature cell biology	Publication Date: Apr 26, 2021
Citations: 99	License type: cc-by

Affiliation: QB3, University of California, Berkeley

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.

Highlights

Macroautophagy is the means by which eukaryotic cells degrade and recycle large objects such as molecular aggregates, organelles, and intracellular pathogens 1
Autophagy consists of the initiation and growth of a double membrane phagophore (a.k.a. “isolation membrane”) around the object to be degraded, followed by the sealing of the phagophore into the double membrane vesicle known as the autophagosome, and its fusion with the lysosome (Fig. 1)
TBK1 facilitates FIP200 recruitment by NDP52, but chemically directed recruitment of FIP200 can bypass the need for cargo-NDP52 engagement, demonstrating that unc-51-like kinase 1 (ULK1) complex recruitment is sufficient to trigger autophagosome biogenesis 29. These findings, coupled with the results described above for p62, show that at least two receptors trigger autophagy initiation by recruiting the ULK1 complex to its site of action

Summary

Introduction

Macroautophagy (henceforward, “autophagy”) is the means by which eukaryotic cells degrade and recycle large objects such as molecular aggregates, organelles, and intracellular pathogens 1. Autophagy consists of the initiation and growth of a double membrane phagophore How these complexes and proteins orchestrate membrane lipids through phagophore initiation, growth, and closure has been a mystery, of “origins unknown, biogenesis complex” 3.

Results

Conclusion