Targeting mitochondria: a new promising approach for the treatment of liver diseases.
Mitochondrial dysfunction acts as a common pathogenetic mechanism in several acute and chronic liver diseases, such as Alcoholic and Non-Alcoholic Fatty Liver Disease (NAFLD), drug-induced steatohepatitis, viral hepatitis, biliary cirrhosis, hepatocellular carcinoma, ischemia/reperfusion injury and transplant rejection. In particular mitochondrial uncoupling,has been recently identified to play a determinant role in the pathogenesis of liver diseases by causing decrease of mitochondrial proton motive force and ATP depletion. Damaged mitochondria present defects in lipid homeostasis, bioenergetics impairment and overproduction of Reactive Oxygen Species (ROS), leading to lipid accumulation and oxidative stress. Dysfunctional and/or uncoupled mitochondria enhance the susceptibility of hepatocytes to cell death by necrosis, via ATP depletion, or by apoptosis, via membrane permeabilization. Thus, prevention of mitochondrial alterations promises to be an effective strategy for treatment of liver diseases. However, no therapy has proven to be absolutely effective, whereas those that are beneficial present several side effects. The present review summarizes the recent approaches in mitochondrial drug deliver systems and focuses on mitochondria-targeted molecules application in liver disease. New selective molecules and nanocarriers technology are also considered as potentially effective in the targeting of mitochondrial dysfunction in liver pathology.
Serviddio
G
G
Centre for the Study of Liver Diseases, Department of Medical and Occupational Sciences, University of Foggia, 71122, Foggia, Italy. g.serviddio@unifg.it
Bellanti
F
F
Sastre
J
J
Vendemiale
G
G
Altomare
E
E
D000818:Animals; D016923:Cell Death / Q000502:physiology; D016503:Drug Delivery Systems / Q000379:methods*; D006801:Humans; D008107:Liver Diseases / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism
D017382:Reactive Oxygen Species