Mitochondrial function and malfunction in the pathophysiology of pancreatitis.
As a primary energy producer, mitochondria play a fundamental role in pancreatic exocrine physiology and pathology. The most frequent aetiology of acute pancreatitis is either gallstones or heavy alcohol consumption. Repeated episodes of acute pancreatitis can result in the development of chronic pancreatitis and increase the lifetime risk of pancreatic cancer 100-fold. Pancreatic cancer is one of the most common causes of cancer mortality with only about 3-4 % of patients surviving beyond 5 years. It has been shown that acute pancreatitis involves Ca²⁺ overload and overproduction of reactive oxygen species in pancreatic acinar cells. Both factors significantly affect mitochondria and lead to cell death. The pathogenesis of inflammation in acute and chronic pancreatitis is tightly linked to the induction of necrosis and apoptosis. There is currently no specific therapy for pancreatitis, but recent findings of an endogenous protective mechanism against Ca²⁺ overload--and particularly the potential to boost this protection--bring hope of new therapeutic approaches.
MRC Group, School of Biosciences, Biomedical Sciences Building, Museum Avenue, Cardiff, CF10 3AX, Wales, UK. GerasimenkoOV@cardiff.ac.uk
Oleg V
OV
Gerasimenko
Julia V
JV
Gerasimenko
D061354:Acinar Cells / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling; D006801:Humans; D008928:Mitochondria / Q000378:metabolism*; D033681:Mitochondrial Membrane Transport Proteins / Q000378:metabolism; D000083162:Mitochondrial Permeability Transition Pore; D009336:Necrosis; D018384:Oxidative Stress; D010179:Pancreas / Q000378:metabolism; D010195:Pancreatitis / Q000209:etiology*; D053499:Plasma Membrane Calcium-Transporting ATPases / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D050998:bcl-2 Homologous Antagonist-Killer Protein / Q000378:metabolism
D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D017382:Reactive Oxygen Species; D050998:bcl-2 Homologous Antagonist-Killer Protein; D053499:Plasma Membrane Calcium-Transporting ATPases; D002118:Calcium