USP9x is required in VMP1-related autophagosome biogenesis

FELIPE RENNA; MARÍA INÉS VACCARO; MARIANA TADIC; DANIEL GRASSO; TAMARA ORQUERA

CABA

Workshop; Redox mechanisms in pathophysiology; 2018

Facultad de Farmacia y Bioquímica, 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-related protein whose expression is essential for autophagosome biogenesis and its expression is induced by pancreatitis. VMP1 mediates zymophagy, a protective selective type of autophagy-mediated degradation of zymogen granules that prevents the spreading of activated enzymes within pancreas tissue. 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. By immunofluorescence, USP9x presents a cytoplasmic diffuse pattern at basal conditions, and it relocates after 15 min of starvation to a perinuclear area (48.0% ± 1.2 vs 40.5% ± 1.9 p