The VMP1-Beclin 1 interaction regulates autophagy induction
Open Access
- 11 January 2013
- journal article
- research article
- Published by Springer Science and Business Media LLC in Scientific Reports
- Vol. 3 (1), srep01055
- https://doi.org/10.1038/srep01055
Abstract
The Vacuole Membrane Protein 1 -VMP1- is a pancreatitis-associated transmembrane protein whose expression triggers autophagy in several human diseases. In the current study, we unveil the mechanism through which this protein induces autophagosome formation in mammalian cells. We show that VMP1 autophagy-related function requires its 20-aminoacid C-terminus hydrophilic domain (VMP1-AtgD). This is achieved through its direct binding to the BH3 motif of Beclin 1 leading to the formation of a complex with the Class III phosphatidylinositol-3 kinase (PI3K) hVps34, a key positive regulator of autophagy, at the site where autophagosomes are generated. This interaction also concomitantly promotes the dissociation of Bcl-2, an autophagy inhibitor, from Beclin 1. Moreover, we show that the VMP1-Beclin 1-hVps34 complex favors the association of Atg16L1 and LC3 with the autophagosomal membranes. Collectively, these findings reveal that VMP1 expression recruits and activates the Class III PI3K complex at the site of autophagosome formation during mammalian autophagy.This publication has 45 references indexed in Scilit:
- Exercise-induced BCL2-regulated autophagy is required for muscle glucose homeostasisNature, 2012
- Zymophagy, a Novel Selective Autophagy Pathway Mediated by VMP1-USP9x-p62, Prevents Pancreatic Cell Death*Journal of Biological Chemistry, 2011
- Eaten alive: a history of macroautophagyNature, 2010
- Mammalian autophagy: core molecular machinery and signaling regulationCurrent Opinion in Cell Biology, 2010
- A subdomain of the endoplasmic reticulum forms a cradle for autophagosome formationNature, 2009
- Distinct regulation of autophagic activity by Atg14L and Rubicon associated with Beclin 1–phosphatidylinositol-3-kinase complexNature, 2009
- Identification of Barkor as a mammalian autophagy-specific factor for Beclin 1 and class III phosphatidylinositol 3-kinaseProceedings of the National Academy of Sciences of the United States of America, 2008
- JNK1-Mediated Phosphorylation of Bcl-2 Regulates Starvation-Induced AutophagyMolecular Cell, 2008
- Autophagosome formation: core machinery and adaptationsNature, 2007
- Suppression of basal autophagy in neural cells causes neurodegenerative disease in miceNature, 2006