Title: Autophagosome formation from membrane compartments enriched in phosphatidylinositol 3-phosphate and dynamically connected to the endoplasmic reticulum
Authors: Axe, Elizabeth L
Walker, Simon A
Manifava, Maria
Chandra, Priya
Roderick, H Llewelyn
Habermann, Anja
Griffiths, Gareth
Ktistakis, Nicholas T # ×
Issue Date: Aug-2008
Publisher: Rockefeller Institute Press
Series Title: Journal of Cell Biology vol:182 issue:4 pages:685-701
Abstract: Autophagy is the engulfment of cytosol and organelles by double-membrane vesicles termed autophagosomes. Autophagosome formation is known to require phosphatidylinositol 3-phosphate (PI(3)P) and occurs near the endoplasmic reticulum (ER), but the exact mechanisms are unknown. We show that double FYVE domain-containing protein 1, a PI(3)P-binding protein with unusual localization on ER and Golgi membranes, translocates in response to amino acid starvation to a punctate compartment partially colocalized with autophagosomal proteins. Translocation is dependent on Vps34 and beclin function. Other PI(3)P-binding probes targeted to the ER show the same starvation-induced translocation that is dependent on PI(3)P formation and recognition. Live imaging experiments show that this punctate compartment forms near Vps34-containing vesicles, is in dynamic equilibrium with the ER, and provides a membrane platform for accumulation of autophagosomal proteins, expansion of autophagosomal membranes, and emergence of fully formed autophagosomes. This PI(3)P-enriched compartment may be involved in autophagosome biogenesis. Its dynamic relationship with the ER is consistent with the idea that the ER may provide important components for autophagosome formation.
ISSN: 0021-9525
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Experimental Cardiology
× corresponding author
# (joint) last author

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