Mitochondria-associated programmed cell death in pancreatic β cell of T2DM

Mitochondria, as essential organelles that integrate energy metabolism and intracellular signaling, have recently gained increasing attention in the study of pancreatic β-cell dysfunction in type 2 diabetes mellitus (T2DM). Programmed death of β-cells is recognized as a mechanism contributing to both disease progression and remission, primarily by impairing insulin secretion and disrupting glucose homeostasis. Accumulating evidence indicates that mitochondria serve as central hubs coordinating multiple programmed cell death (PCD) pathways. Structural or functional abnormalities of mitochondria initiate β-cell loss through distinct molecular mechanisms. This review systematically summarizes recent advances in understanding mitochondria-associated PCD in β-cells and its contribution to T2DM pathophysiology. Four major forms of PCD, including apoptosis, necroptosis, ferroptosis, and pyroptosis, are described in detail, highlighting their mitochondrial triggers and molecular signatures. Moreover, emerging mitochondrial-targeted therapeutic strategies are discussed, which aim to attenuate β-cell death and preserve functional mass. A better understanding of these processes may facilitate the development of novel therapeutic interventions to delay the onset and progression of T2DM and its related complications.