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Mitochondrial abnormalities\u2014such as impaired oxidative phosphorylation (OXPHOS), dysregulated tricarboxylic acid (TCA) cycle, excessive reactive oxygen species (ROS) production, and altered mitochondrial dynamics\u2014can contribute to IR by oxidatively modifying insulin-signaling proteins and activating inflammatory pathways (JNK\/NF-\u03baB). Recent work also implicates microRNAs (miRNAs) as modulators that link mitochondrial function and redox balance to insulin action; however, their magnitude and tissue specificity in human T2DM remain to be defined. Therapeutic strategies that target mitochondrial bioenergetics and redox homeostasis show promise, while miRNA-directed approaches are emerging. This review provides an explanatory synthesis aimed at distinguishing associations within the mitochondria-ROS-insulin resistance axis supported by solid evidence from findings influenced by specific contexts, and outlines translational opportunities and their associated delivery bottlenecks.<\/jats:p>","DOI":"10.3389\/fendo.2025.1674477","type":"journal-article","created":{"date-parts":[[2025,12,17]],"date-time":"2025-12-17T06:44:55Z","timestamp":1765953895000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":39,"title":["Mitochondrial bioenergetics dysfunction in T2DM: linking oxidative stress to insulin 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