title: Mitochondrial mechanisms of death responses in pancreatitis.
abstract: Pancreatitis is a severe and frequently lethal disorder, a major cause of which is alcohol abuse. Parenchymal cell death is a major complication of pancreatitis. In experimental models of acute pancreatitis, acinar cells have been shown to die through both necrosis and apoptosis, the two principal pathways of cell death. The severity of experimental acute pancreatitis correlates directly with the extent of necrosis and inversely with apoptosis. Thus, understanding the regulation of apoptosis and necrosis is becoming exceedingly important in investigations of the pathogenesis and treatment of pancreatitis. Over the past decade, the mitochondria have emerged as a master regulator of cell death in various physiological and pathological processes. Release of mitochondrial cytochrome c into the cytosol is a central event in apoptosis, whereas mitochondrial depolarization resulting in ATP depletion leads to necrosis. The present review focuses on the mitochondrial mechanisms of death responses in pancreatitis, with emphasis on mitochondrial membrane permeabilization and its role in the balance between apoptosis and necrosis in acute pancreatitis, and alcohol's effects on death responses of pancreatitis.
authors.affiliation: USC-UCLA Research Center for Alcoholic Liver and Pancreatic Diseases, VA Greater Los Angeles Healthcare System and University of California, Los Angeles, California 90073, USA.
authors.forename: Irina V
authors.initials: IV
authors.lastname: Odinokova
authors.forename: Kai-Feng
authors.initials: KF
authors.lastname: Sung
authors.forename: Olga A
authors.initials: OA
authors.lastname: Mareninova
authors.forename: Kip
authors.initials: K
authors.lastname: Hermann
authors.forename: Ilya
authors.initials: I
authors.lastname: Gukovsky
authors.forename: Anna S
authors.initials: AS
authors.lastname: Gukovskaya
mesh_terms: D017209:Apoptosis; D016923:Cell Death; D006801:Humans; D008928:Mitochondria / Q000502:physiology*; D009336:Necrosis; D010195:Pancreatitis / Q000378:metabolism / Q000473:pathology*