Distinct autophagosomal-lysosomal fusion mechanism revealed by thapsigargin-induced autophagy arrest Journal Article

   

Authors:	Ganley, I.; Wong, P. M.; Gammoh, N.; Jiang, X.
Article Title:	Distinct autophagosomal-lysosomal fusion mechanism revealed by thapsigargin-induced autophagy arrest
Abstract:	Autophagy, a catabolic pathway that delivers cellular components to lysosomes for degradation, can be activated by stressful conditions such as nutrient starvation and endoplasmic reticulum (ER) stress. We report that thapsigargin, an ER stressor widely used to induce autophagy, in fact blocks autophagy. Thapsigargin does not affect autophagosome formation but leads to accumulation of mature autophagosomes by blocking autophagosome fusion with the endocytic system. Strikingly, thapsigargin has no effect on endocytosis-mediated degradation of epidermal growth factor receptor. Molecularly, while both Rab7 and Vps16 are essential regulatory components for endocytic fusion with lysosomes, we found that Rab7 but not Vps16 is required for complete autophagy flux, and that thapsigargin blocks recruitment of Rab7 to autophagosomes. Therefore, autophagosomal-lysosomal fusion must be governed by a distinct molecular mechanism compared to general endocytic fusion. © 2011 Elsevier Inc.
Keywords:	controlled study; nonhuman; animal cell; mouse; protein degradation; epidermal growth factor receptor; regulatory mechanism; autophagy; endocytosis; lysosome; rab7 protein; thapsigargin; autophagosome
Journal Title:	Molecular Cell
Volume:	42
Issue:	6
ISSN:	1097-2765
Publisher:	Cell Press
Date Published:	2011-06-24
Start Page:	731
End Page:	743
Language:	English
DOI:	10.1016/j.molcel.2011.04.024
PROVIDER:	scopus
PMCID:	PMC3124681
PUBMED:	21700220
DOI/URL:	http://www.scopus.com/inward/record.url?eid=2-s2.0-79959346132&partnerID=40&md5=05dff0cbf3165a24b3ce6717df7395cb
Notes:	--- - "Export Date: 17 August 2011" - "CODEN: MOCEF" - "Source: Scopus"

https://synapse.mskcc.org/synapse/works/has_related_data_chk/9434