Oxidative phosphorylation and breast cancer progression: insights into PGC-1α's role in mitochondrial function

Breast cancer still ranks high as a leading cause of mortality in women due to its complex relationship with metabolic reprogramming and tumor progression. The peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α), a key transcriptional coactivator regulating mitochondrial biogenesis and oxidative phosphorylation (OXPHOS), plays a dual role in breast cancer metabolism. On the one hand, PGC-1α enhances mitochondrial function and energy production, facilitating tumor survival and metastasis, particularly in hypoxic environments. On the other hand, its suppression can limit tumor aggressiveness and energy metabolism. This dual functionality underscores its context-dependent role in cancer progression, where its activation or inhibition varies across tumor subtypes and microenvironmental conditions. The purpose of this review is to provide a comprehensive understanding of PGC-1α's dual roles in breast cancer, elucidating its regulation of mitochondrial function, its contribution to tumor progression, and the therapeutic implications of targeting this key metabolic regulator.