Mitochondrial superoxide/hydrogen peroxide: An emerging therapeutic target for metabolic diseases

Mitochondria are well known for their roles as energy and metabolic factory. Mitochondrial reactive oxygen species (mtROS) refer to superoxide anion radical (•O2−) and hydrogen peroxide (H2O2). They are byproducts of electron transport in mitochondrial respiratory chain and are implicated in the regulation of physiological and pathological signal transduction. Especially when mitochondrial •O2−/H2O2 production is disturbed, this disturbance is closely related to the occurrence and development of metabolic diseases. In this review, the sources of mitochondrial •O2−/H2O2 as well as mitochondrial antioxidant mechanisms are summarized. Furthermore, we particularly emphasize the essential role of mitochondrial •O2−/H2O2 in metabolic diseases. Specifically, perturbed mitochondrial •O2−/H2O2 regulation aggravates the progression of metabolic diseases, including diabetes, gout and nonalcoholic fatty liver disease (NAFLD). Given the deleterious effect of mitochondrial •O2−/H2O2 in the development of metabolic diseases, antioxidants targeting mitochondrial •O2−/H2O2 might be an attractive therapeutic approach for the prevention and treatment of metabolic diseases.