Genetic factors related to mitochondrial function and risk of diabetes mellitus

Mitochondria are the intracellular organelles responsible for the generation of ATP by the process of oxidative phosphorylation (OXPHOS) and have their own DNA containing genes for 13 subunits of OXPHOS and 2 rRNAs and 22 tRNAs for their protein synthesis machinery. Since mitochondrial DNA (mtDNA) has limited coding capacity, nuclear genes make a major contribution to mitochondrial architecture, metabolic systems and biogenesis. Nowadays, there is a growing body of evidence that the mitochondrial dysfunction plays a crucial role in the pathogenesis of type 2 diabetes. In this review, we showed that mtDNA copy number in peripheral blood cells is associated with various pathophysiological characteristics of type 2 diabetes such as insulin resistance and insulin secretory defect. In addition, peripheral blood mtDNA copy number is a risk factor for the development of type 2 diabetes. Common polymorphisms in mtDNA and nuclear genes regulating mitochondrial function might be associated with type 2 diabetes. Elucidation of genetic factors regulating mitochondrial function would be of help to understand how mitochondrial dysfunction is linked to the pathogenesis of type 2 diabetes.