Connexins modulate autophagosome biogenesis

Eloy Bejarano, Andrea Yuste, Bindi Patel, Randy F. Randy, David C. Spray, Ana Maria Cuervo

Research output: Contribution to journalArticle

62 Citations (Scopus)

Abstract

The plasma membrane contributes to the formation of autophagosomes, the double-membrane vesicles that sequester cytosolic cargo and deliver it to lysosomes for degradation during autophagy. In this study, we have identified a regulatory role for connexins (Cx), the main components of plasma membrane gap junctions, in autophagosome formation. We have found that plasma-membrane- localized Cx proteins constitutively downregulate autophagy through a direct interaction with several autophagy-related proteins involved in the initial steps of autophagosome formation, such as Atg16 and components of the PI(3)K autophagy initiation complex (Vps34, Beclin-1 and Vps15). On nutrient starvation, this inhibitory effect is released by the arrival of Atg14 to the Cx-Atg complex. This promotes the internalization of Cx-Atg along with Atg9, which is also recruited to the plasma membrane in response to starvation. Maturation of the Cx-containing pre-autophagosomes into autophagosomes leads to degradation of these endogenous inhibitors, allowing for sustained activation of autophagy.

Original languageEnglish (US)
Pages (from-to)401-414
Number of pages14
JournalNature Cell Biology
Volume16
Issue number5
DOIs
StatePublished - 2014

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Connexins
Autophagy
Cell Membrane
Starvation
Gap Junctions
Lysosomes
Down-Regulation
Autophagosomes
Food
Membranes
Proteins

ASJC Scopus subject areas

  • Cell Biology

Cite this

Connexins modulate autophagosome biogenesis. / Bejarano, Eloy; Yuste, Andrea; Patel, Bindi; Randy, Randy F.; Spray, David C.; Cuervo, Ana Maria.

In: Nature Cell Biology, Vol. 16, No. 5, 2014, p. 401-414.

Research output: Contribution to journalArticle

Bejarano, E, Yuste, A, Patel, B, Randy, RF, Spray, DC & Cuervo, AM 2014, 'Connexins modulate autophagosome biogenesis', Nature Cell Biology, vol. 16, no. 5, pp. 401-414. https://doi.org/10.1038/ncb2934
Bejarano, Eloy ; Yuste, Andrea ; Patel, Bindi ; Randy, Randy F. ; Spray, David C. ; Cuervo, Ana Maria. / Connexins modulate autophagosome biogenesis. In: Nature Cell Biology. 2014 ; Vol. 16, No. 5. pp. 401-414.
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