The Complex Interplay between Imbalanced Mitochondrial Dynamics and Metabolic Disorders in Type 2 Diabetes

Abstract

Type 2 diabetes mellitus (T2DM) is a global burden, with an increasing number of people affected and increasing treatment costs. The advances in research and guidelines improve the management of blood glucose and related diseases, but T2DM and its complications are still a big challenge in clinical practice. T2DM is a metabolic disorder in which insulin signaling is impaired from reaching its effectors. Mitochondria are the “powerhouses” that not only generate the energy as adenosine triphosphate (ATP) using pyruvate supplied from glucose, free fatty acid (FFA), and amino acids (AA) but also regulate multiple cellular processes such as calcium homeostasis, redox balance, and apoptosis. Mitochondrial dysfunction leads to various diseases, including cardiovascular diseases, metabolic disorders, and cancer. The mitochondria are highly dynamic in adjusting their functions according to cellular conditions. The shape, morphology, distribution, and number of mitochondria reflect their function through various processes, collectively known as mitochondrial dynamics, including mitochondrial fusion, fission, biogenesis, transport, and mitophagy. These processes determine the overall mitochondrial health and vitality. More evidence supports the idea that dysregulated mitochondrial dynamics play essential roles in the pathophysiology of insulin resistance, obesity, and T2DM, as well as imbalanced mitochondrial dynamics found in T2DM. This review updates and discusses mitochondrial dynamics and the complex interactions between it and metabolic disorders.

Keywords

• fission
• fusion
• metabolic disorders
• mitochondrial biogenesis
• mitochondrial dynamics
• type 2 diabetes mellitus