Multifaceted roles of aerobic glycolysis and oxidative phosphorylation in hepatocellular carcinoma

Liver cancer is a common malignancy with high morbidity and mortality rates. Changes in liver metabolism are key factors in the development of primary hepatic carcinoma, and mitochondrial dysfunction is closely related to the occurrence and development of tumours. Accordingly, the study of the metabolic mechanism of mitochondria in primary hepatic carcinomas has gained increasing attention. A growing body of research suggests that defects in mitochondrial respiration are not generally responsible for aerobic glycolysis, nor are they typically selected during tumour evolution. Conversely, the dysfunction of mitochondrial oxidative phosphorylation (OXPHOS) may promote the proliferation, metastasis, and invasion of primary hepatic carcinoma. This review presents the current paradigm of the roles of aerobic glycolysis and OXPHOS in the occurrence and development of hepatocellular carcinoma (HCC). Mitochondrial OXPHOS and cytoplasmic glycolysis cooperate to maintain the energy balance in HCC cells. Our study provides evidence for the targeting of mitochondrial metabolism as a potential therapy for HCC.

Automated summary

Liver cancer, a common and deadly malignancy, is closely associated with changes in liver metabolism and mitochondrial dysfunction. While defects in mitochondrial respiration are not generally responsible for aerobic glycolysis or selected during tumor evolution, dysfunction of mitochondrial oxidative phosphorylation (OXPHOS) may promote the proliferation, metastasis, and invasion of primary hepatic carcinoma. This review explores the roles of aerobic glycolysis and OXPHOS in the occurrence and development of hepatocellular carcinoma (HCC), highlighting the cooperative nature of mitochondrial OXPHOS and cytoplasmic glycolysis in maintaining energy balance in HCC cells. The findings suggest that targeting mitochondrial metabolism could be a potential therapy for HCC.