Role of Deubiquitinase USP9x as a New Player in the Autophagy Pathway

FELIPE RENNA; VACCARO, MARÍA INÉS; DANIEL GRASSO; TAMARA ORQUERA

CABA

Conferencia; BUENOS AIRES RESEARCH CONFERENCES ON AUTOPHAGY 2017; 2017

IBIMOL (CONICET-UBA)

Intracellular activation of zymogen granules triggers pancreas self-digestion and leads to acute pancreatitis. Most of acute pancreatitis cases are self-limited, suggesting the importance of response mechanisms of acinar cells. VMP1 is an autophagy protein capable of induce autophagy even in non-starved condition. VMP1 is induced by pancreatitis and mediates the zymophagy, a selective type of autophagy-mediated degradation of zymogen granules. Previously we demonstrated that the deubiquitinase USP9x interacts with VMP1 during zymophagy in acute pancreatitis. The aim of this work is to elucidate the role of USP9x in autophagosome formation. We show that shRNA-mediated depletion of USP9x significantly reduces autophagosomes evaluated by LC3-RFP dots per cell in starved HeLa cells (6.8±4.2 vs 33.6±2.4 p