Phagophores evolve from recycling endosomes.


Type
Article
Change log
Authors
Puri, Claudia 
Vicinanza, Mariella 
Rubinsztein, David C 
Abstract

The membrane origins of autophagosomes have been a key unresolved question in the field. The earliest morphologically recognizable structure in the macroautophagy/autophagy itinerary is the double-membraned cup-shaped phagophore. Newly formed phosphatidylinositol 3-phosphate (PtdIns3P) on the membranes destined to become phagophores recruits WIPI2, which, in turn, binds ATG16L1 to define the sites of autophagosome formation. Here we review our recent study showing that membrane recruitment of WIPI2 requires coincident detection of PtdIns3P and RAB11A, a protein that marks recycling endosomes. We found that multiple core autophagy proteins are more tightly associated with the recycling endosome compartment than with endoplasmic reticulum (ER)-mitochondrial contact sites. Furthermore, biochemical isolation of the recycling endosomes confirmed that they recruit autophagy proteins. Finally, fixed and live-cell imaging data revealed that recycling endosomes engulf autophagic substrates. Indeed, the sequestration of mitochondria after mitophagy stimulation depends on early autophagy regulators. These data suggest that autophagosomes evolve from the RAB11A compartment.

Description
Keywords
Autophagosome origin, RAB11, WIPI2, recycling endosome
Journal Title
Autophagy
Conference Name
Journal ISSN
1554-8627
1554-8635
Volume Title
14
Publisher
Informa UK Limited
Sponsorship
Alzheimer's Research UK (ARUK-2015DDI-CAM)
Wellcome Trust (095317/Z/11/Z)
Wellcome Trust (100140/Z/12/Z)