VMP1 dependent selective mitophagy and mitochondrial fragmentation are protective cellular mechanisms in pancreatitis

ROPOLO ALEJANDRO; VACCARO MARÍA INÉS; VANASCO VIRGINIA; ALVAREZ SILVIA; GRASSO DANIEL

Berlin

Congreso; 50TH EPC ? THE JUBILEE MEETING OF THE EUROPEAN PANCREATIC CLUB; 2018

EUROPEAN PANCREATIC CLUB

Mitophagy, an autophagy pathway that selectively degrades damaged mitochondria, is an early cellular event in acute pancreatitis (AP). Mitochondria are the major source of ATP and other biological molecules, which are necessary for autophagy, and they also are the main cellular source of reactive O2 species (ROS). Nitric oxide (NO) and ROS are thought to regulate mitophagy during pancreatitis. The aim was to analyze mitochondrial dysfunction and dynamics during selective autophagy induced by AP in animal and cellular models, and to evaluate the cellular redox state in this context. Animal model, female Sprague-Dawley rats (45 days old) were ip injected with 50 mg/kg caerulein (CAE) during 1h intervals. Autophagy induced by AP was analysed through VMP1, P62 and LC3 expression. For mitochondrial dynamics, OPA1 and DRP1 expressions were determined. OPA1 expression (mitochondrial fusion protein) was found decreased after 1 h of pancreatitis. However, a time-dependent increase was observed up to 48 h. Moreover, no expression of DRP1 (mitochondrial fission protein) was observed during the first 24 h of PA. Mitochondrial respiration and ATP production were measured in order to evaluate mitochondrial function. Mitochondrial O2 consumption and ATP production decreased by 35% and 70% respectively (CG: 40±5 ng-atO/min.mg protein; 140±18 nmol ATP/ min.mg.protein, P