A novel mammalian trans-membrane protein reveals an alternative initiation pathway for autophagy.

Autophagy is an early cellular event during acute pancreatitis, a disease defined as pancreas self-digestion. The Vacuole Membrane Protein 1 (VMP1) is a trans-membrane protein highly activated in acinar cells early during pancreatitis-induced autophagy and it remains in the autophagosomal membrane. We have shown that VMP1 expression is able to trigger autophagy in mammalian cells, even under nutrient-replete conditions. VMP1 is induced by autophagy stimuli and its expression is required for autophagosome development. VMP1 interacts with Beclin 1 through its hydrophilic C-terminal region, which we named Atg domain, as it is essential for autophagy. Remarkably, VMP1 pancreas-specific transgenic expression in mice promotes autophagosome formation. Most of the autophagy-related proteins were described in yeast or have a yeast homologue. VMP1 does not have any known homologue in yeast but its expression is required to start the autophagic process in mammalian cells. These findings support the hypothesis that mammalian cells may regulate autophagy in a different way. We propose that VMP1 is a novel autophagy related trans-membrane protein, which may lead the way in the search for alternative mechanisms of autophagosome formation.