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Atg8 family LC3/GABARAP proteins are crucial for autophagosome–lysosome fusion but not autophagosome formation during PINK1/Parkin mitophagy and starvation

Nguyen, Thanh Ngoc, Padman, Benjamin Scott, Usher, Joanne, Oorschot, Viola, Ramm, Georg, Lazarou, Michael·2016·Journal of Cell Biology
DOI 10.1083/jcb.201607039PMC PMC5166504
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Abstract

Members of the Atg8 family of proteins are conjugated to autophagosomal membranes, where they have been proposed to drive autophagosome formation and selective sequestration of cargo. In mammals, the Atg8 family consists of six members divided into the LC3 and GABARAP subfamilies. To define Atg8 function, we used genome editing to generate knockouts of the LC3 and GABARAP subfamilies as well as all six Atg8 family members in HeLa cells. We show that Atg8s are dispensable for autophagosome formation and selective engulfment of mitochondria, but essential for autophagosome–lysosome fusion. We find that the GABARAP subfamily promotes PLEKHM1 recruitment and governs autophagosome–lysosome fusion, whereas the LC3 subfamily plays a less prominent role in these processes. Although neither GABARAPs nor LC3s are required for autophagosome biogenesis, loss of all Atg8s yields smaller autophagosomes and a slowed initial rate of autophagosome formation. Our results clarify the essential function of the Atg8 family and identify GABARAP subfamily members as primary contributors to PINK1/Parkin mitophagy and starvation autophagy.

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Metadata

Authors
Nguyen, T. N., Padman, B. S., Usher, J., Oorschot, V., Ramm, G., & Lazarou, M.
Affiliations
  • Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Melbourne, Victoria 3800, Australia 1
  • Monash Ramaciotti Centre for Cryo Electron Microscopy, Monash University, Melbourne, Victoria 3800, Australia 2
ORCID
Venue
Journal of Cell Biology
Publisher
Rockefeller University Press
Published
2016-11-18
Volume
215
Issue
6
Pages
857-874
ISSN
  • 0021-9525
  • 1540-8140
DOI
10.1083/jcb.201607039
PMC
PMC5166504
Cited by
668
References
15
Language
en
Funders
National Health and Medical Research Council (GNT1063781, GNT1106471)

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