IMR Press / FBE / Volume 4 / Issue 6 / DOI: 10.2741/e539

Frontiers in Bioscience-Elite (FBE) is published by IMR Press from Volume 13 Issue 2 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on imrpress.com as a courtesy and upon agreement with Frontiers in Bioscience.

Open Access Review

Mitochondrial dysfunction in cholestatic liver diseases

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1 Department of Physiology, School of Pharmacy, University of Valencia, Valencia, Spain
2 Department of Medical and Occupational Sciences, University of Foggia, Foggia, Italy
3 Centro Nacional de Investigaciones Cardiovasculares, Consejo Superior de Investigaciones Cientificas, CNIC, CSIC, Madrid, Spain

Academic Editor: Marcelo Gabriel Roma

Front. Biosci. (Elite Ed) 2012, 4(6), 2233–2252; https://doi.org/10.2741/e539
Published: 1 January 2012
(This article belongs to the Special Issue Experimental and clinical cholestasis)
Abstract

Cholestatic liver diseases are characterized by blockade of bile flow from the liver to the intestine, and accumulation of hydrophobic bile acids in the liver and plasma. As a consequence an inflammatory response evolves associated with increased apoptosis, oxidative stress, and eventually fibrosis. Cholestasis is associated with profound metabolic changes, alterations in the mitochondrial function, decreased fatty acid oxidation, and increased glycolisis. Mitochondria play a central role in the development of this liver disease because they mediate death receptor signaling - triggered by inflammatory cytokines or bile acids - and contribute to oxidative damage, metabolic disorder, and onset of fibrosis. During the pathogenesis of biliary cirrhosis mitochondria’s need for renewal is hampered by a blunted mitochondrial biogenesis. Lack of stimulation of mitochondrial renewal helps to explain mitochondrial impairment in long-term cholestasis. The marked depletion of mitochondrial DNA and occurrence of mitochondrial DNA deletions are probably relevant contributors to the progression of this severe disease. All these findings certainly support the consideration of long-term cholestasis as a secondary mitochondrial hepatopathy.

Keywords
Mitochondrial function
Bile acids
Apoptosis
Oxidative stress
Review
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