Mitochondrial dynamics in diabetic peripheral neuropathy: Pathogenesis, progression, and therapeutic approaches

Diabetic peripheral neuropathy (DPN) is a chronic complication resulting from late-stage peripheral nerve damage in diabetes. It is associated with pain and can lead to foot ulcers and even amputations. Currently, there are no reversible treatments for DPN. The pathophysiology of DPN is extremely complex and involves multiple mediating factors. Despite extensive research by scholars worldwide, the exact mechanisms underlying DPN remain incompletely understood. Recent evidence increasingly supports the notion that dysregulation of mitochondrial fission and fusion proteins, which regulate mitochondrial morphology and quantity in neurons under hyperglycemic conditions, may be a key pathological mechanism of DPN. In fact, processes such as metabolism, energy production, inflammation, reactive oxygen species generation, and apoptosis rely on the balance between fission and fusion. Pathological alterations in this balance can lead to bioenergetic dysfunction and mitochondrial-mediated cell death, thus contributing to the progression of DPN. Mitochondria regulate their number, quality, and function through mitochondrial dynamics (fission and fusion) to maintain homeostasis and cope with structural and functional impairments under high-glucose conditions. This article discusses the pathophysiological changes in DPN, the role of mitochondrial dynamics in its pathogenesis, and current targeted mitochondrial therapies, aiming to enhance the understanding of the mechanisms involved in DPN and to explore more effective treatment methods and intervention strategies.