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Early endosomes and endosomal coatomer are required for autophagy

Autophagy, an intracellular degradative pathway, maintains cell homeostasis under normal and stress conditions. Nascent double-membrane autophagosomes sequester and enclose cytosolic components and organelles, and subsequently fuse with the endosomal pathway allowing content degradation. Autophagy r...

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Detalles Bibliográficos
Autores principales: Razi, Minoo, Chan, Edmond Y.W., Tooze, Sharon A.
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2009
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2700373/
https://www.ncbi.nlm.nih.gov/pubmed/19364919
http://dx.doi.org/10.1083/jcb.200810098
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author Razi, Minoo
Chan, Edmond Y.W.
Tooze, Sharon A.
author_facet Razi, Minoo
Chan, Edmond Y.W.
Tooze, Sharon A.
author_sort Razi, Minoo
collection PubMed
description Autophagy, an intracellular degradative pathway, maintains cell homeostasis under normal and stress conditions. Nascent double-membrane autophagosomes sequester and enclose cytosolic components and organelles, and subsequently fuse with the endosomal pathway allowing content degradation. Autophagy requires fusion of autophagosomes with late endosomes, but it is not known if fusion with early endosomes is essential. We show that fusion of AVs with functional early endosomes is required for autophagy. Inhibition of early endosome function by loss of COPI subunits (β′, β, or α) results in accumulation of autophagosomes, but not an increased autophagic flux. COPI is required for ER-Golgi transport and early endosome maturation. Although loss of COPI results in the fragmentation of the Golgi, this does not induce the formation of autophagosomes. Loss of COPI causes defects in early endosome function, as both transferrin recycling and EGF internalization and degradation are impaired, and this loss of function causes an inhibition of autophagy, an accumulation of p62/SQSTM-1, and ubiquitinated proteins in autophagosomes.
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spelling pubmed-27003732009-10-20 Early endosomes and endosomal coatomer are required for autophagy Razi, Minoo Chan, Edmond Y.W. Tooze, Sharon A. J Cell Biol Research Articles Autophagy, an intracellular degradative pathway, maintains cell homeostasis under normal and stress conditions. Nascent double-membrane autophagosomes sequester and enclose cytosolic components and organelles, and subsequently fuse with the endosomal pathway allowing content degradation. Autophagy requires fusion of autophagosomes with late endosomes, but it is not known if fusion with early endosomes is essential. We show that fusion of AVs with functional early endosomes is required for autophagy. Inhibition of early endosome function by loss of COPI subunits (β′, β, or α) results in accumulation of autophagosomes, but not an increased autophagic flux. COPI is required for ER-Golgi transport and early endosome maturation. Although loss of COPI results in the fragmentation of the Golgi, this does not induce the formation of autophagosomes. Loss of COPI causes defects in early endosome function, as both transferrin recycling and EGF internalization and degradation are impaired, and this loss of function causes an inhibition of autophagy, an accumulation of p62/SQSTM-1, and ubiquitinated proteins in autophagosomes. The Rockefeller University Press 2009-04-20 /pmc/articles/PMC2700373/ /pubmed/19364919 http://dx.doi.org/10.1083/jcb.200810098 Text en © 2009 Razi et al. 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.jcb.org/misc/terms.shtml). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).
spellingShingle Research Articles
Razi, Minoo
Chan, Edmond Y.W.
Tooze, Sharon A.
Early endosomes and endosomal coatomer are required for autophagy
title Early endosomes and endosomal coatomer are required for autophagy
title_full Early endosomes and endosomal coatomer are required for autophagy
title_fullStr Early endosomes and endosomal coatomer are required for autophagy
title_full_unstemmed Early endosomes and endosomal coatomer are required for autophagy
title_short Early endosomes and endosomal coatomer are required for autophagy
title_sort early endosomes and endosomal coatomer are required for autophagy
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2700373/
https://www.ncbi.nlm.nih.gov/pubmed/19364919
http://dx.doi.org/10.1083/jcb.200810098
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