Type 1 diabetes mellitus: Inflammation, mitophagy, and mitochondrial function

Type 1 diabetes mellitus (T1DM) is a T-cell-mediated autoimmune disease characterized by the damage of insulin-secreting β-cells in the pancreatic islets of Langerhans. To date, its etiology is not fully understood, despite decades of active search for root causes, and that underlines the complexity of the disease pathogenesis. It was found that mitophagy plays a regulatory role in the development of autoimmune response during T1DM pathogenesis by preventing the accumulation of defective/dysfunctional mitochondria in pancreatic cells. Mitochondrial dysfunction due to impaired mitophagy with the release of mitochondrial reactive oxygen species (mtROS) and mitochondrial DNA (mtDNA) contributes to initiating an inflammatory response by elevating pro-inflammatory cytokines and interacting with receptors like those involved in the pathogen-associated response. Moreover, mtROS and mtDNA activate pathways leading to the development of chronic inflammation, which is tightly implicated in T1DM autoimmunity. In this review, we summarized the evidence highlighting the functional role of mitophagy and mitochondria in the development of immune response and chronic inflammation during T1DM pathogenesis. Several anti-inflammatory and mitophagy-related treatment options have been explored.