Mitochondrial Homeostasis in Pancreatic β Cell Function: Mechanisms and Therapeutic Targets for Diabetes.

Abstract

Mitochondrial homeostasis is essential for pancreatic β cell function, and its disruption underlies diabetes pathogenesis. Chronic hyperglycemia, lipotoxicity, and inflammation impair mitochondrial quality control (MQC), leading to β cell dysfunction, oxidative stress, and apoptosis. Mitochondria-organelle interactions, particularly with the endoplasmic reticulum (ER), lysosomes, and Golgi apparatus, further exacerbate β cell dysfunction by disrupting calcium signaling and metabolic coordination. Emerging potential therapies, such as DRAK2 inhibitors and metabolic reprogramming agents, show promise in preserving MQC and β cell function. However, clinical validation is needed. This review highlights mitochondrial dysfunction as a central driver of diabetes and underscores the potential of mitochondrial-targeted strategies for therapeutic intervention.