Mitochondrial transplantation therapy inhibits the proliferation of malignant hepatocellular carcinoma and its mechanism

• Published in: Mitochondrion 2022-07, Vol.65, p.11-22
• Main Authors: Zhou, Wei, Zhao, Zizhen, Yu, Zhenyao, Hou, Yixue, Keerthiga, Rajendiran, Fu, Ailing
• Format: Article
• Language: English
• Subjects: Apoptosis; Cell cycle arrest; Hepatocellular carcinoma; Mitochondrial therapy
• ISSN: 1567-7249; 1872-8278
• DOI: 10.1016/j.mito.2022.04.004

•The study suggests that healthy mitochondria can inhibit the proliferation of malignant hepatocellular carcinoma.•The study finds that the anti-tumor mechanism of the mitochondria would be associated to reduction of aerobic glycolysis, which would decrease the energy supply of tumors.•The mitochondria could down-regulate the expression of cycle-related proteins while up-regulate apoptosis-related proteins in tumor cells.•The study suggests that mitochondrial transplantation therapy would be a potential biotechnology for preventing tumor. Mitochondrial dysfunction plays a vital role in growth and malignancy of tumors. In recent scenarios, mitochondrial transplantation therapy is considered as an effective method to remodel mitochondrial function in mitochondria-related diseases. However, the mechanism by which mitochondrial transplantation blocks tumor cell proliferation is still not determined. In addition, mitochondria are maternal inheritance in evolution, and mitochondria obtained from genders exhibit differences in mitochondrial activity. Therefore, the study indicates the inhibitory effect of mitochondria from different genders on hepatocellular carcinoma and explores the molecular mechanism. The results reveal that the healthy mitochondria can retard the proliferation of the hepatocellular carcinoma cells in vitro and in vivo through arresting cell cycle and inducing apoptosis. The molecular mechanism suggests that mitochondrial transplantation therapy can decrease aerobic glycolysis, and down-regulate the expression of cycle-related proteins while up-regulate apoptosis-related proteins in tumor cells. In addition, the antitumor activity of mitochondria from female mice (F-Mito) is relatively higher than that of mitochondria from male mice (M-Mito), which would be related to the evidence that the F-Mito process higher activity than the M-Mito. This study clarifies the mechanism of exogenous mitochondria inhibiting the proliferation of hepatocellular carcinoma and contributes a new biotechnology for therapy of mitochondria-related diseases from different genders.