Early endosomes and endosomal coatomer are required for autophagy

M. Razi, Edmond Y. Chan, Sharon A. Tooze

Research output: Contribution to journalArticle

175 Citations (Scopus)

Abstract

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.
LanguageEnglish
Pages305-321
Number of pages17
JournalJournal of Cell Biology
Volume185
Issue number2
DOIs
Publication statusPublished - 20 Apr 2009

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Endosomes
Autophagy
Coat Protein Complex I
Ubiquitinated Proteins
Recycling
Transferrin
Epidermal Growth Factor
Organelles
Homeostasis
Autophagosomes
Membranes

Keywords

  • autophagy
  • cell homeostasis
  • Nascent double-membrane autophagosomes
  • autophagosomes
  • endosomes

Cite this

Razi, M. ; Chan, Edmond Y. ; Tooze, Sharon A. / Early endosomes and endosomal coatomer are required for autophagy. In: Journal of Cell Biology. 2009 ; Vol. 185, No. 2. pp. 305-321.
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Early endosomes and endosomal coatomer are required for autophagy. / Razi, M.; Chan, Edmond Y.; Tooze, Sharon A.

In: Journal of Cell Biology, Vol. 185, No. 2, 20.04.2009, p. 305-321.

Research output: Contribution to journalArticle

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