1INSERM, Univ Rennes, INRAE, Institut NUMECAN (Nutrition Metabolisms and Cancer) UMR_A 1341, UMR_S 1241, F-35000 Rennes, France. Electronic address: firstname.lastname@example.org.
2Department of Endocrinology and Diabetology, Medical Faculty and University Hospital Düsseldorf, Heinrich-Heine University Düsseldorf, Düsseldorf, Germany; Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich-Heine University Düsseldorf, Düsseldorf, Germany; German Center for Diabetes Research, Partner Düsseldorf, München-Neuherberg, Germany. Electronic address: email@example.com.
Fatty liver diseases increasingly arise from common metabolic diseases, but also from xenobiotics and excessive alcohol use. Despite different etiology, they share several similarities regarding their toxic effects on hepatic mitochondrial functionality and dynamics. Invasive or complex methodology limits large-scale investigations of mitochondria in human livers. Nevertheless, abnormal mitochondrial function, such as impaired fatty acid oxidation and oxidative phosphorylation, drives oxidative stress and is an important feature of human steatohepatitis. On the other hand, hepatic mitochondria can be flexible and adapt to the ambient metabolic condition to prevent from triglyceride and lipotoxin accumulation in obesity. Experience from studies of xenobiotic effects provided important insights into the regulation of hepatic mitochondria. Increasing awareness of the joint presence of metabolic disease-related (lipotoxic) and alcohol-related liver diseases further highlights the need to better understand their mutual interaction and potentiation regarding disease progression. Recent clinical studies assessed effects of diets or bariatric surgery on liver mitochondria, which are also currently evolving as interesting target to treat non-alcoholic fatty liver disease by using liver-directed thyroid hormone receptor agonists or protonophores. This review summarizes the current knowledge on hepatic mitochondria with a focus on fatty liver diseases due to obesity, type 2 diabetes and xenobiotics.