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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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Formato: | Texto |
Lenguaje: | English |
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The Rockefeller University Press
2009
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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. |
format | Text |
id | pubmed-2700373 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2009 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT raziminoo earlyendosomesandendosomalcoatomerarerequiredforautophagy AT chanedmondyw earlyendosomesandendosomalcoatomerarerequiredforautophagy AT toozesharona earlyendosomesandendosomalcoatomerarerequiredforautophagy |