Abstract:

Hepatocellular carcinoma （HCC） is a malignancy associated with high global incidence and mortality rates， whose development and progression are closely linked to metabolic dysregulation. As central hubs for cellular energy metabolism and signaling， mitochondria undergo extensive and complex remodeling in HCC， profoundly influencing tumor initiation， progression， and therapeutic response. However， the specific mechanisms underlying these mitochondrial changes and their exact roles in HCC pathogenesis remain incompletely elucidated， which has， to a certain extent， impeded the development and clinical application of mitochondria-targeted therapeutics for HCC. This review systematically summarized mitochondrial alterations in HCC from three key dimensions： metabolic reprogramming， oxidative stress and mitochondrial DNA （mtDNA） damage， and dysregulation of mitochondrial dynamics. It further elucidated the mechanisms by which these alterations drive HCC development and treatment response. Additionally， the review consolidated and prospected the current progress on mitochondria-targeted therapeutic strategies for HCC， aiming provide theoretical foundation and novel insights for future basic research and clinical interventions in the treatment of HCC.

Key words: hepatocellular carcinoma, mitochondria, mitochondrial dynamics, targeted therapeatics