Targeting mitochondria: a great boon to fight type 2 diabetes

Abstract

Type 2 diabetes is a chronic metabolic disease characterized by the development of low-grade systemic inflammation, hyperglycaemia, and hyperlipidaemia. These pathogenic traits have a profound impact on mitochondrial function as mitochondria serve as intermediary organelles between nutrients and energy production. Moreover, the mitochondrial quality control system is also altered and rendered defective by type 2 diabetes. These alterations entail the accumulation of defective mitochondria, which causes the diabetic background to deteriorate further. In this context, it is of paramount importance to improve mitochondrial function and ameliorate the consequences of mitochondrial dysfunction. This review assesses different treatments that target mitochondrial dysfunction as a way of treating type 2 diabetes. Lifestyle interventions and pharmacological treatments such as biguanides, thiazolidinediones, a-glucosidase inhibitors, glucagon-like peptide 1 receptor agonists, or sodium-glucose co-transporter-2 inhibitors protect mitochondrial function, while novel mitochondria-targeted molecules including natural compounds, mitochondria-targeted antioxidants, inhibitors of mitochondria pore transition pore opening, NO and H2S donors, and inhibitors of mitochondrial fission positively impact on mitochondrial function and its quality control mechanisms. Most of these therapeutic tools require more research, but they already show promising therapeutic mechanisms that improve type 2 diabetes and its cellular consequences.