期刊
AUTOPHAGY
卷 14, 期 8, 页码 1475-1477出版社
TAYLOR & FRANCIS INC
DOI: 10.1080/15548627.2018.1482148
关键词
Autophagosome origin; recycling endosome; RAB11; WIPI2
类别
资金
- UK Dementia Research Institute (Medical Research Council)
- UK Dementia Research Institute (Alzheimer's Research UK)
- UK Dementia Research Institute (Alzheimer's Society)
- Wellcome Trust [095317/Z/11/Z]
- MRC [UKDRI-2002] Funding Source: UKRI
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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据