The VMP1-Beclin 1 Interaction Regulates Autophagy Induction

MOLEJON MI; VACCARO MI

Oslo

Congreso; EMBO Conferences on Autophagy; 2013

EMBO

The VMP1-Beclin 1 Interaction Regulates Autophagy InductionMaria I Molejon, Alejandro Ropolo, Maria I VaccaroThe vacuole membrane protein 1 -VMP1- is an essential autophagy related transmembrane protein conserved from worms to mammals. VMP1 triggers autophagosome formation even under nutrient-replete conditions. In the current study, we unveil the mechanism through which this protein induces autophagy in mammalian cells. We show that VMP1 autophagy-related function requires its C-terminus domain (Atg domain). This is achieved through its binding to the BH3 of Beclin 1 and this interaction concomitantly promotes the dissociation of Bcl-2, an autophagy inhibitor, from Beclin 1. VMP1-Beclin1 interaction leads to the formation of a complex with the Class III phosphatidyl-3 kinase complex, a key positive regulator of autophagy. Our findings indicate that VMP1-Beclin 1 interaction promotes the localization of other Atg proteins to the autophagosomal membrane. We show that the VMP1-Beclin 1 complex promotes PI3P generation on autophagosomal membranes, acting upstream of the Atg16L1 complex during autophagy. Collectively, these findings reveal that VMP1, through its Atg domain, regulates autophagy induction in mammalian cells promoting the recruitment of Class III PI3K complex at the site of autophagosome formation.