Oxidative stress, cardiolipin and mitochondrial dysfunction in nonalcoholic fatty liver disease.

Abstract

Nonalcoholic fatty liver disease (NAFLD) is today considered the most common form of chronic liver disease, affecting a high proportion of the population worldwide. NAFLD encompasses a large spectrum of liver damage, ranging from simple steatosis to steatohepatitis, advanced fibrosis and cirrhosis. Obesity, hyperglycemia, type 2 diabetes and hypertriglyceridemia are the most important risk factors. The pathogenesis of NAFLD and its progression to fibrosis and chronic liver disease is still unknown. Accumulating evidence indicates that mitochondrial dysfunction plays a key role in the physiopathology of NAFLD, although the mechanisms underlying this dysfunction are still unclear. Oxidative stress is considered an important factor in producing lethal hepatocyte injury associated with NAFLD. Mitochondrial respiratory chain is the main subcellular source of reactive oxygen species (ROS), which may damage mitochondrial proteins, lipids and mitochondrial DNA. Cardiolipin, a phospholipid located at the level of the inner mitochondrial membrane, plays an important role in several reactions and processes involved in mitochondrial bioenergetics as well as in mitochondrial dependent steps of apoptosis. This phospholipid is particularly susceptible to ROS attack. Cardiolipin peroxidation has been associated with mitochondrial dysfunction in multiple tissues in several physiopathological conditions, including NAFLD. In this review, we focus on the potential roles played by oxidative stress and cardiolipin alterations in mitochondrial dysfunction associated with NAFLD.

• Authors: Giuseppe Paradies, Valeria Paradies, Francesca M Ruggiero, Giuseppe Petrosillo
• Journal: World journal of gastroenterology (World J Gastroenterol) Vol. 20 Issue 39 Pg. 14205-18 (Oct 21 2014) ISSN: 2219-2840 [Electronic] United States
• PMID: 25339807 (Publication Type: Journal Article, Review)

Chemical References

• Antioxidants
• Cardiolipins
• DNA, Mitochondrial
• Electron Transport Chain Complex Proteins
• Reactive Oxygen Species

Topics

• Animals
• Antioxidants (therapeutic use)
• Apoptosis
• Cardiolipins (metabolism)
• DNA Damage
• DNA, Mitochondrial (metabolism)
• Electron Transport Chain Complex Proteins (metabolism)
• Humans
• Lipid Peroxidation
• Liver (drug effects, metabolism, pathology, physiopathology)
• Mitochondria, Liver (drug effects, metabolism)
• Mitochondrial Diseases (drug therapy, metabolism, pathology, physiopathology)
• Non-alcoholic Fatty Liver Disease (drug therapy, metabolism, pathology, physiopathology)
• Oxidative Stress (drug effects)
• Protein Carbonylation
• Reactive Oxygen Species (metabolism)