Tumor mitochondria alter their functions to reprogram cell metabolism and then allow tumor cells to rapidly proliferate in the hypoxic and acidic microenvironment. However, roles of normal mitochondria played in tumor progression are still unclear. Here we investigate the normal mitochondrial effect on abnormal metabolism of tumors, and to clarify why the mitochondria have to undergo functional changes in the tumor growth. The mitochondria isolated from healthy mouse livers were intravenously injected into melanoma model mice with lung metastasis, then the tumor growth, animal survival and associated metabolic changes were studied. The results reveal that the mitochondria significantly retard tumor growth and increase survival days of animals. The anti-tumor effect of the mitochondria is related to interfering the tumor cell metabolisms, such as reducing glycolysis and producing an oxidative intracellular environment, all of which are not suitable for tumor cell proliferation. In addition, the mitochondria increases cell apoptosis, necrosis, and mitophagy. These effects are more efficient with the mitochondria isolated from young mouse livers than those from aged mice. Our study not only provides a valuable approach to invest mitochondrial function associated with tumor growth but also offer new insight into tumor therapy through interfering the tumor cell metabolism by healthy mitochondria.

Changes in mitochondrial structure and function are mostly responsible for aging and age-related features. Whether healthy mitochondria could prevent aging is, however, unclear. Here we intravenously injected the mitochondria isolated from young mice into aged mice and investigated the mitotherapy on biochemistry metabolism and animal behaviors. The results showed that heterozygous mitochondrial DNA (mtDNA) of both aged and young mouse coexisted in tissues of aged mice after mitochondrial administration, and meanwhile, ATP content in tissues increased while reactive oxygen species (ROS) level reduced. Besides, the mitotherapy significantly improved cognitive and motor performance of aged mice. Our study, at the first report in aged animals, not only provides a useful approach to study mitochondrial function associated with aging, but also a new insight into anti-aging through mitotherapy.

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Today mitochondria are considered much more than a energy plant in cells. Mitochondrial transplantation therapy has been an active research area for treating mitochondria-associated diseases from animal studies to clinical trials. However, the specific mechanism involved in the anti-tumor activity of healthy mitochondria remain to be characterized. Here we investigate the signal mechanism and gender difference of mitochondrial transplantation therapy against malignant melanoma. In the study, we administrated intact mitochondria extracted from mouse livers respectively to the mice bearing malignantly subcutaneous and metastatic melanoma, and identified the signal mechanism responsible for the mitochondrial treatment through transcriptomic analysis. Meanwhile, the efficiency of female mitochondria and male mitochondria was compared in the cultured melanoma cells and transplanted melanoma in mice. The results suggested that the mitochondria significantly inhibited the tumor cell proliferation in vitro through cell cycle arrest and induction of cell apoptosis. In the melanoma-bearing mice, the mitochondria retard the tumor growth and lung migration, and the transcriptomic analysis indicated that general chromosome silencing was strongly associated with the mitochondria against melanoma after the mitochondrial transplantation on the metastasis melanoma. Moreover, the anti-tumor activity of mitochondria from female animals was more efficient in comparison to the males, and the female mitochondria could probably induce more persuasive mitochondria-nuclear communication than the mitochondria from male mice. The study identifies the anti-tumor mechanism of the mitochondrial transplantation therapy, and provides a novel insight into the effect of mitochondria from different gender.

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