Role of Mitochondria dynamics during selective autophagy induced by acute pancreatitis.

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

San Diego, California

Congreso; 46th Meeting of the American Pancreatic Association; 2015

American Pancreatic Association,

We have previously demonstrated the selective autophagic pathway zymophagy as an early protective mechanism in acute pancreatitis (AP). Zymophagy impairment during AP, promotes cell damage and probably the progression of the disease. ATP and other molecules necessary in cellular stress processes are provided by mitochondria. Thus, a normal mitochondrial bioenergetics would be necessary for zymophagy in response to the disease. The aim of this study is to analyze the mitochondrial dynamics and function during selective autophagy induced by acute pancreatitis. Female Sprague-Dawley rats (45 days old) were ip injected with caerulein (CAE) 50 mg/kg in 1h intervals. Treated groups studied: CAE 1, animals sacrificed 1 hour after first injection; CAE 3, animals sacrificed after 3h treatment; CAE 24 and CAE 48, animals injected with 7 doses and sacrificed at 24 and 48 h respectively. Control groups (CG) were injected with vehicle. Zymophagy induced by AP was confirmed by VMP1 expression, Trypsinogen/LC3 and Trypsinogen/Lamp2 colocalizations as well as p62 degradation. Between 1 and 24 hours of experimental pancreatitis, 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 < 0.01). CAE48 shows control values in both parameters. On the other hand, OPA1 expression (mitochondrial fusion protein) is significantly decreased after 1 h of pancreatitis, but it increases in a time course towards 48 hours. Moreover, no expression of DRP1 (mitochondrial fission protein) is observed during the first 24 hours of pancreatitis. Our results show mitochondrial dysfunction during experimental pancreatitis, which recovers after 48 hours. Data also show the increment of OPA1 suggesting mitochondria elongation, which avoids degradation as a mitochondria preservation mechanism during acute pancreatitis induced zymophagy.