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Current Drug Targets
ISSN (Print): 1389-4501
ISSN (Online): 1873-5592
VOLUME: 12
ISSUE: 6
DOI: 10.2174/138945011795528877      Price:  $58









Mitochondria in Chronic Liver Disease

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Author(s): Ignazio Grattagliano, Stefan Russmann, Catia Diogo, Leonilde Bonfrate, Paulo J. Oliveira, David Q.-H. Wang and Piero Portincasa
Pages 879-893 (15)
Abstract:
Mitochondria are the main energy source in hepatocytes and play a major role in extensive oxidative metabolism and normal function of the liver. This key role also assigns mitochondria a gateway function in the center of signaling pathways that mediate hepatocyte injury, because impaired mitochondrial functions affect cell survival and contribute to the onset and perpetuation of liver diseases. Altered mitochondrial functions have indeed been documented in a variety of chronic liver diseases including alcohol-induced liver disease, nonalcoholic fatty liver disease, viral hepatitis, primary and secondary cholestasis, hemochromatosis, and Wilsons disease. Major changes include impairment of the electron transport chain and/or oxidative phosphorylation leading to decreased oxidative metabolism of various substrates, decreased ATP synthesis, and reduced hepatocyte tolerance towards stressing insults. Functional impairment of mitochondria is often accompanied by structural changes, resulting in organelle swelling and formation of inclusions in the mitochondrial matrix. Adequate mitochondrial functions in hepatocytes are maintained by mitochondrial proliferation and/or increased activity of critical enzymes. The assessment of mitochondrial functions in vivo can be a useful tool in liver diseases for diagnostic and prognostic purposes, and also for the evaluation of (novel) therapeutic interventions.
Keywords:
Alcohol, cholestasis, fatty liver, hemochromatosis, hepatitis C virus, nitrosative stress, nonalcoholic fatty liver disease, disease, primary biliary cirrhosis, Wilson's disease, oxidative stress
Affiliation:
University of Bari Medical School, Clinica Medica “A. Murri”, Department of Internal and PublicMedicine (DIMIMP), Hospital Policlinico - 70124 Bari, Italy.