Role of mitochondria in nonalcoholic fatty liver disease-from origin to propagation

ObjectivesMitochondria play a major role in cell energy-generating processes and integrate several signalling pathways to control cellular life and death.Design and methodsSeveral liver diseases are characterized by mitochondrial alterations which are directly or indirectly dependent on the activation of intracellular stress cascades or receptor-mediated pathways. This article examines the role of mitochondrial dysfunction in critical initiating or propagating events in fatty liver infiltration and nonalcoholic fatty liver disease (NAFLD). Genetic variants and the role of drug-induced toxicity have been considered.ResultsKey alterations of mitochondrial physiology associated with hepatocyte fatty changes are described. The value of novel non-invasive diagnostic methods to detect mitochondrial metabolic alterations is also discussed.ConclusionsMitochondrial metabolic remodeling is a predominant factor in the appearance and perpetuation of hepatocyte fat accumulation. Non-invasive techniques to identify mitochondrial dysfunction and proper mitochondria protection are two necessary clinical steps for an efficient management of NAFLD.

Schematic representation of the participation of the liver and mitochondria in particular to systemic metabolic changes occurring in NAFLD as a part of the metabolic syndrome. Both genetic variants and environmental factors contribute to the appearance of the clinical condition. Events include increased synthesis of triglycerides, increased β-oxidation of free fatty acids (FFAs), impaired energy balance, increased oxidative stress and concomitant decrease of antioxidant defences.Figure optionsDownload as PowerPoint slideHighlights
► Mitochondrial changes are key factors in the onset and perpetuation of NAFLD.
► Bioenergetic deficit due to mitochondrial damage compromises hepatocyte recovery.
► Mitochondrial oxidative/nitrosative stress participate to hepatocyte fatty changes.
► Some genes potentially involved in NAFLD may interfere with mitochondrial function.
► Mitochondrial function can be reliable assessed in vivo by specific breath tests.