The multifaceted roles of mitochondria and their therapeutic transformation: a new perspective on triple-negative breast cancer treatment

Triple-negative breast cancer (TNBC) represents the most aggressive breast cancer subtype, lacking effective targeted therapies and exhibiting pronounced therapeutic resistance. Mitochondria have recently emerged as central regulators of TNBC pathogenesis, functioning beyond their traditional roles as cellular powerhouses. This article synthesizes current understanding of how mitochondrial metabolic reprogramming-particularly the synergistic hyperactivation of oxidative phosphorylation, fatty acid oxidation, and glutamine metabolism-drives TNBC progression, metastasis, and chemoresistance. We further examine the dichotomous roles of mitochondrial dynamics and mitophagy in shaping tumor cell fate, and explore how mitochondria orchestrate diverse programmed cell death pathways and immune modulation. Translational strategies targeting mitochondrial vulnerabilities, including small-molecule inhibitors, nanomaterial-based delivery systems, and combination regimens, are critically evaluated. Despite significant preclinical promise, challenges including tumor selectivity, metabolic plasticity, and clinical translation remain. By integrating mechanistic insights with emerging therapeutic innovations, this perspective highlights the transformative potential of mitochondria-targeted interventions for future TNBC management.