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Early endosomes and endosomal coatomer are required for autophagy
Correspondence to Sharon A. Tooze: sharon.tooze{at}cancer.org.uk
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
) 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.
Abbreviations used in this paper: ARF, ADP-ribosylation factor; Atg, autophagy related; AV, autophagic vacuole; COP, coat protein complex; EEA1, early endosomal autoantigen 1; ERGIC-53, ER-Golgi intermediate compartment 53 kD; GM130, Golgi membrane protein 130 kD; LAMP, lysosomal-associated membrane protein; LTR, Lysotracker red; MPR, mannose-6-phosphate receptor; MVB, multi-vesicular body; Tfn, transferrin; Ub, ubiquitin.
© 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/).
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