Mitochondrial Dynamics in Diabetes Mellitus and Its Complications: Mechanisms, Pathological Roles, and Therapeutic...

Diabetes mellitus (DM) is a progressive metabolic disorder in which mitochondrial dysfunction is increasingly recognized as a central contributor to metabolic deterioration and diabetic complications. However, whether dysregulated mitochondrial dynamics represents a primary pathogenic driver, an adaptive response, or a consequence of metabolic stress remains incompletely understood. This review summarizes current advances in the molecular mechanisms governing mitochondrial fission, fusion, and mitophagy, with particular emphasis on their coordinated roles in mitochondrial quality control rather than isolated morphological changes. We discuss how disrupted mitochondrial dynamics contributes to pancreatic β-cell dysfunction, insulin resistance, diabetic nephropathy (DN), diabetic cardiomyopathy (DCM), diabetic retinopathy (DR), and diabetic osteoporosis (DOP) through context-dependent regulation of oxidative stress, bioenergetics, inflammation, and endoplasmic reticulum-mitochondria crosstalk. Furthermore, we critically evaluate emerging therapeutic strategies, including metformin, sodium-glucose cotransporter 2 inhibitors, mitochondrial fission inhibitors, and mitochondria-targeted antioxidants, highlighting both their therapeutic potential and current translational challenges. We propose that restoring the physiological equilibrium among mitochondrial fission, fusion, and mitophagy, rather than unidirectionally inhibiting a single pathway, represents a more promising strategy for preventing and treating diabetes and its complications.