Decoding the mitochondrial metabolic engine for tumor metastasis and clinical therapeutic opportunities

Mitochondrial metabolic reprogramming, a recognized cancer hallmark, plays a pivotal role in malignant progression. These organelles serve as the cell's metabolic hubs, coordinating essential processes including OXPHOS, the TCA cycle, and FAO. This review delineates the significant alterations and functions of mitochondrial reprogramming in tumor metastasis, encompassing mechanisms such as energy restructuring and EMT promotion. Furthermore, mitochondrial dynamics exert profound effects on mitochondrial morphology and function, thereby reprogramming cellular metabolism to facilitate tumor metastasis. This review also explores the substantial mitochondrial metabolic changes within the TME and their interplay in optimizing energy utilization, forming the pre-metastatic niche, and sculpting an immunosuppressive milieu. Finally, it provides a critical evaluation of current and emerging therapeutic strategies targeting mitochondrial metabolism, including their use in combination regimens and the application of novel nano-delivery platforms.