Alterations in mitochondrial function and morphology in chronic liver disease: pathogenesis and potential for therapeutic intervention.

Studies assessing mitochondrial function and structure in livers from humans or experimental animals with chronic liver disease, including liver cirrhosis, revealed a variety of alterations in comparison with normal subjects or control animals. Depending on the etiology of chronic liver disease, the function of the electron transport chain and/or ATP synthesis was found to be impaired, leading to decreased oxidative metabolism of various substrates and to impaired recovery of the hepatic energy state after a metabolic insult. Changes in mitochondrial structure include megamitochondria with reduced cristae, dilatation of mitochondrial cristae and crystalloid inclusions in the mitochondrial matrix. The most important strategies to maintain an adequate mitochondrial function per liver are mitochondrial proliferation and increases in the activity of critical enzymes or in the content of cofactors per mitochondrion. Possibilities to assess hepatic mitochondrial function and to treat mitochondrial dysfunction in patients with chronic liver disease are discussed.