Mitochondrial involvement in non-alcoholic steatohepatitis

Gaetano Serviddio, Juan Sastre, Francesco Bellanti, José Viña, Gianluigi Vendemiale, Emanuele Altomare

Research output: Contribution to journalArticle

Abstract

Non-alcoholic steatohepatitis (NASH) is an increasing recognized condition that may progress to end-stage liver disease. There are consistent evidences that mitochondrial dysfunction plays a central role in NASH whatever its origin. Mitochondria are the key controller of fatty acids removal and this is part of an intensive gene program that modifies hepatocytes to counteract the excessive fat storage. Mitochondrial dysfunction participates at different levels in NASH pathogenesis since it impairs fatty liver homeostasis and induces overproduction of ROS that in turn trigger lipid peroxidation, cytokines release and cell death. In this review we briefly recall the role of mitochondria in fat metabolism and energy homeostasis and focus on the role of mitochondrial impairment and uncoupling proteins in the pathophysiology of NASH progression. We suggest that mitochondrial respiratory chain, UCP2 and redox balance cooperate in a common pathway that permits to set down the mitochondrial redox pressure, limits the risk of oxidative damage, and allows the maximal rate of fat removal. When the environmental conditions change and high energy supply occurs, hepatocytes are unable to replace their ATP store and steatosis progress to NASH and cirrhosis. The beneficial effects of some drugs on mitochondrial function are also discussed.

Original languageEnglish
Pages (from-to)22-35
Number of pages14
JournalMolecular Aspects of Medicine
Volume29
Issue number1-2
DOIs
Publication statusPublished - Feb 2008

Keywords

  • ATP homeostasis
  • Fatty liver
  • HNE
  • Mitochondria
  • NASH
  • Reactive oxygen species
  • UCP2

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Molecular Medicine

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  • Cite this

    Serviddio, G., Sastre, J., Bellanti, F., Viña, J., Vendemiale, G., & Altomare, E. (2008). Mitochondrial involvement in non-alcoholic steatohepatitis. Molecular Aspects of Medicine, 29(1-2), 22-35. https://doi.org/10.1016/j.mam.2007.09.014