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Dynamic and transient interactions of Atg9 with autophagosomes, but not membrane integration, are required for autophagy

Autophagy is a catabolic process essential for cell homeostasis, at the core of which is the formation of double-membrane organelles called autophagosomes. Atg9 is the only known transmembrane protein required for autophagy and is proposed to deliver membrane to the preautophagosome structures and a...

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Autores principales: Orsi, A., Razi, M., Dooley, H. C., Robinson, D., Weston, A. E., Collinson, L. M., Tooze, S. A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3350551/
https://www.ncbi.nlm.nih.gov/pubmed/22456507
http://dx.doi.org/10.1091/mbc.E11-09-0746
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author Orsi, A.
Razi, M.
Dooley, H. C.
Robinson, D.
Weston, A. E.
Collinson, L. M.
Tooze, S. A.
author_facet Orsi, A.
Razi, M.
Dooley, H. C.
Robinson, D.
Weston, A. E.
Collinson, L. M.
Tooze, S. A.
author_sort Orsi, A.
collection PubMed
description Autophagy is a catabolic process essential for cell homeostasis, at the core of which is the formation of double-membrane organelles called autophagosomes. Atg9 is the only known transmembrane protein required for autophagy and is proposed to deliver membrane to the preautophagosome structures and autophagosomes. We show here that mammalian Atg9 (mAtg9) is required for the formation of DFCP1-positive autophagosome precursors called phagophores. mAtg9 is recruited to phagophores independent of early autophagy proteins, such as ULK1 and WIPI2, but does not become a stable component of the autophagosome membrane. In fact, mAtg9-positive structures interact dynamically with phagophores and autophagosomes without being incorporated into them. The membrane compartment enriched in mAtg9 displays a unique sedimentation profile, which is unaltered upon starvation-induced autophagy. Correlative light electron microscopy reveals that mAtg9 is present on tubular–vesicular membranes emanating from vacuolar structures. We show that mAtg9 resides in a unique endosomal-like compartment and on endosomes, including recycling endosomes, where it interacts with the transferrin receptor. We propose that mAtg9 trafficking through multiple organelles, including recycling endosomes, is essential for the initiation and progression of autophagy; however, rather than acting as a structural component of the autophagosome, it is required for the expansion of the autophagosome precursor.
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spelling pubmed-33505512012-07-30 Dynamic and transient interactions of Atg9 with autophagosomes, but not membrane integration, are required for autophagy Orsi, A. Razi, M. Dooley, H. C. Robinson, D. Weston, A. E. Collinson, L. M. Tooze, S. A. Mol Biol Cell Articles Autophagy is a catabolic process essential for cell homeostasis, at the core of which is the formation of double-membrane organelles called autophagosomes. Atg9 is the only known transmembrane protein required for autophagy and is proposed to deliver membrane to the preautophagosome structures and autophagosomes. We show here that mammalian Atg9 (mAtg9) is required for the formation of DFCP1-positive autophagosome precursors called phagophores. mAtg9 is recruited to phagophores independent of early autophagy proteins, such as ULK1 and WIPI2, but does not become a stable component of the autophagosome membrane. In fact, mAtg9-positive structures interact dynamically with phagophores and autophagosomes without being incorporated into them. The membrane compartment enriched in mAtg9 displays a unique sedimentation profile, which is unaltered upon starvation-induced autophagy. Correlative light electron microscopy reveals that mAtg9 is present on tubular–vesicular membranes emanating from vacuolar structures. We show that mAtg9 resides in a unique endosomal-like compartment and on endosomes, including recycling endosomes, where it interacts with the transferrin receptor. We propose that mAtg9 trafficking through multiple organelles, including recycling endosomes, is essential for the initiation and progression of autophagy; however, rather than acting as a structural component of the autophagosome, it is required for the expansion of the autophagosome precursor. The American Society for Cell Biology 2012-05-15 /pmc/articles/PMC3350551/ /pubmed/22456507 http://dx.doi.org/10.1091/mbc.E11-09-0746 Text en © 2012 Orsi et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0). “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society of Cell Biology.
spellingShingle Articles
Orsi, A.
Razi, M.
Dooley, H. C.
Robinson, D.
Weston, A. E.
Collinson, L. M.
Tooze, S. A.
Dynamic and transient interactions of Atg9 with autophagosomes, but not membrane integration, are required for autophagy
title Dynamic and transient interactions of Atg9 with autophagosomes, but not membrane integration, are required for autophagy
title_full Dynamic and transient interactions of Atg9 with autophagosomes, but not membrane integration, are required for autophagy
title_fullStr Dynamic and transient interactions of Atg9 with autophagosomes, but not membrane integration, are required for autophagy
title_full_unstemmed Dynamic and transient interactions of Atg9 with autophagosomes, but not membrane integration, are required for autophagy
title_short Dynamic and transient interactions of Atg9 with autophagosomes, but not membrane integration, are required for autophagy
title_sort dynamic and transient interactions of atg9 with autophagosomes, but not membrane integration, are required for autophagy
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3350551/
https://www.ncbi.nlm.nih.gov/pubmed/22456507
http://dx.doi.org/10.1091/mbc.E11-09-0746
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