Mitochondria‐Mediated Pathogenesis and Therapeutics for Non‐Alcoholic Fatty Liver Disease

Non‐alcoholic fatty liver disease (NAFLD) has become a worldwide epidemic over the last decade. Remarkable progress has been made in understanding the pathogenesis of NAFLD and, subsequently, in developing medications to treat this disease. Although the mechanisms of NAFLD are complex and multifactorial, accumulating and emerging evidence indicates that mitochondria play a critical role in the pathogenesis and progression of NAFLD. Pharmacologic therapies acting on mitochondria may therefore pave the way to novel strategies for the prevention and protection against NAFLD. This review focuses on new insights into the role of hepatic mitochondrial dysfunction in NAFLD, and summarizes recent studies on mitochondria‐centric therapies for NAFLD utilizing new medications or repurposing of currently available drugs. Although some studies presented may feature controversial results or are still in lack of clinical verification, it is undoubted that medications that may spare the mitochondria from multiple levels of damage are highly promising, and have begun to be used with some degree of success. Mitochondria play a critical role in pathogenesis of non‐alcoholic fatty liver disease (NAFLD). Mitochondrial dysfunction promotes steatosis, fatty acid peroxidation and reactive oxygen species (ROS) overproduction, which finally activate inflammation. NAFLD therapeutics from a mitochondria‐centric perspective may be promising. These mitochondria‐centric therapies include antioxidants targeting ROS, agonists or inhibitors targeting key mitochondrial enzymes, and regulators involved in signaling pathways.