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ATG2 transports lipids to promote autophagosome biogenesis

During macroautophagic stress, autophagosomes can be produced continuously and in high numbers. Many different organelles have been reported as potential donor membranes for this sustained autophagosome growth, but specific machinery to support the delivery of lipid to the growing autophagosome memb...

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Autores principales: Valverde, Diana P., Yu, Shenliang, Boggavarapu, Venkata, Kumar, Nikit, Lees, Joshua A., Walz, Thomas, Reinisch, Karin M., Melia, Thomas J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Rockefeller University Press 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6548141/
https://www.ncbi.nlm.nih.gov/pubmed/30952800
http://dx.doi.org/10.1083/jcb.201811139
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author Valverde, Diana P.
Yu, Shenliang
Boggavarapu, Venkata
Kumar, Nikit
Lees, Joshua A.
Walz, Thomas
Reinisch, Karin M.
Melia, Thomas J.
author_facet Valverde, Diana P.
Yu, Shenliang
Boggavarapu, Venkata
Kumar, Nikit
Lees, Joshua A.
Walz, Thomas
Reinisch, Karin M.
Melia, Thomas J.
author_sort Valverde, Diana P.
collection PubMed
description During macroautophagic stress, autophagosomes can be produced continuously and in high numbers. Many different organelles have been reported as potential donor membranes for this sustained autophagosome growth, but specific machinery to support the delivery of lipid to the growing autophagosome membrane has remained unknown. Here we show that the autophagy protein, ATG2, without a clear function since its discovery over 20 yr ago, is in fact a lipid-transfer protein likely operating at the ER–autophagosome interface. ATG2A can bind tens of glycerophospholipids at once and transfers lipids robustly in vitro. An N-terminal fragment of ATG2A that supports lipid transfer in vitro is both necessary and fully sufficient to rescue blocked autophagosome biogenesis in ATG2A/ATG2B KO cells, implying that regulation of lipid homeostasis is the major autophagy-dependent activity of this protein and, by extension, that protein-mediated lipid transfer across contact sites is a principal contributor to autophagosome formation.
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spelling pubmed-65481412019-12-28 ATG2 transports lipids to promote autophagosome biogenesis Valverde, Diana P. Yu, Shenliang Boggavarapu, Venkata Kumar, Nikit Lees, Joshua A. Walz, Thomas Reinisch, Karin M. Melia, Thomas J. J Cell Biol Research Articles During macroautophagic stress, autophagosomes can be produced continuously and in high numbers. Many different organelles have been reported as potential donor membranes for this sustained autophagosome growth, but specific machinery to support the delivery of lipid to the growing autophagosome membrane has remained unknown. Here we show that the autophagy protein, ATG2, without a clear function since its discovery over 20 yr ago, is in fact a lipid-transfer protein likely operating at the ER–autophagosome interface. ATG2A can bind tens of glycerophospholipids at once and transfers lipids robustly in vitro. An N-terminal fragment of ATG2A that supports lipid transfer in vitro is both necessary and fully sufficient to rescue blocked autophagosome biogenesis in ATG2A/ATG2B KO cells, implying that regulation of lipid homeostasis is the major autophagy-dependent activity of this protein and, by extension, that protein-mediated lipid transfer across contact sites is a principal contributor to autophagosome formation. Rockefeller University Press 2019-06-28 2019-04-05 /pmc/articles/PMC6548141/ /pubmed/30952800 http://dx.doi.org/10.1083/jcb.201811139 Text en © 2019 Valverde et al. http://www.rupress.org/terms/https://creativecommons.org/licenses/by-nc-sa/4.0/This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Research Articles
Valverde, Diana P.
Yu, Shenliang
Boggavarapu, Venkata
Kumar, Nikit
Lees, Joshua A.
Walz, Thomas
Reinisch, Karin M.
Melia, Thomas J.
ATG2 transports lipids to promote autophagosome biogenesis
title ATG2 transports lipids to promote autophagosome biogenesis
title_full ATG2 transports lipids to promote autophagosome biogenesis
title_fullStr ATG2 transports lipids to promote autophagosome biogenesis
title_full_unstemmed ATG2 transports lipids to promote autophagosome biogenesis
title_short ATG2 transports lipids to promote autophagosome biogenesis
title_sort atg2 transports lipids to promote autophagosome biogenesis
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6548141/
https://www.ncbi.nlm.nih.gov/pubmed/30952800
http://dx.doi.org/10.1083/jcb.201811139
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