IBIMOL   23987
INSTITUTO DE BIOQUIMICA Y MEDICINA MOLECULAR PROFESOR ALBERTO BOVERIS
Unidad Ejecutora - UE
artículos
Título:
The VMP1-Beclin 1 interaction regulates autophagy induction
Autor/es:
MOLEJÓN MI; ROPOLO A; LO RE A; BOGGIO V; VACCARO MI
Revista:
Scientific Reports
Editorial:
NATURE PUBLISHING GROUP
Referencias:
Lugar: Londres; Año: 2013 vol. 3 p. 1 - 11
ISSN:
2045-2322
Resumen:
The VMP1-Beclin 1 interaction regulates autophagy induction
Maria I. Molejon, Alejandro Ropolo, Andrea Lo Re, Veronica Boggio & Maria I. Vaccaro
Scientific Reports 3, Article number: 1055 doi:10.1038/srep01055The 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.