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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...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The American Society for Cell Biology
2012
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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. |
format | Online Article Text |
id | pubmed-3350551 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | The American Society for Cell Biology |
record_format | MEDLINE/PubMed |
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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