The Pancreatitis-induced Vacuole Membrane Protein 1 Triggers Autophagy in Mammalian Cells. (citado 54 veces al 2/Nov/12)

ROPOLO A; GRASSO D; PARDO R; SACCHETTI ML; ARCHANGE C; LO RE A; SEUX M; NOWAK J; GONZALEZ CD; IOVANNA JL; VACCARO MI

JOURNAL OF BIOLOGICAL CHEMISTRY

The American Society for Biochemistry and Molecular Biology

Lugar: Bethesda, MD, USA.; Año: 2007 vol. 282 p. 37124 - 37133

0021-9258

Al 2/Nov/2012 este trabajo (publicado en diciembre de 2007) fue citado 54 veces según Scopus que al 2 de nov de 2012 marca un indice h de 14, sobre 46 trabajos indexados.Autophagy is a degradation process of cytoplasmic cellular constituents, which serves as a survival mechanism in starving cells, and it is characterized by sequestration of bulk cytoplasm and organelles in double-membrane vesicles called autophagosomes. Autophagy has been linked to a variety of pathological processes such as neurodegenerative diseases and tumorigenesis, which highlights its biological and medical importance. We have previously characterized the vacuole membrane protein 1 (VMP1) gene, which is highly activated in acute pancreatitis, a disease associated with morphological changes resembling autophagy. Here we show that VMP1 expression triggers autophagy in mammalian cells.VMP1expression induces the formation of ultrastructural features of autophagy and recruitment of the microtubule-associated protein 1 light-chain 3 (LC3), which is inhibited after treatment with the autophagy inhibitor 3-methiladenine. VMP1 is induced by starvation and rapamycin treatments. Its expression is necessary for autophagy, because VMP1 small interfering RNA inhibits autophagosome formation under both autophagic stimuli. VMP1 is a transmembrane protein that co-localizes with LC3, a marker of the autophagosomes. It interacts with Beclin 1, a mammalian autophagy initiator, through the VMP1-Atg domain, which is essential forautophagosome formation. VMP1 endogenous expression colocalizes with LC3 in pancreas tissue undergoing pancreatitisinduced autophagy. Finally, VMP1 stable expression targeted topancreas acinar cell in transgenic mice induces autophagosome formation. Our results identify VMP1 as a novel autophagy-related membrane protein involved in the initial steps of the mammaliancell autophagic process.