Healthy Mitochondria: The Brake of Cell Proliferation of Malignant Melanoma

Abstract Background: Melanoma has become the leading cause of death from skin disease, and male patients show higher mortality rate than female. Mitochondrial transplantation therapy is an active area of current research but the anti-melanoma activity and specific mechanism involved in the therapy remain to be fully characterized.Methods: In the study, we intravenously administrated mitochondria extracted from male and female 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. Results: The results suggested that the mitochondria significantly inhibited the tumor growth, and the transcriptomic analysis suggested that general chromosome silencing and local opening of UPRmt effect region were strongly associated with the mitochondria against melanoma., which represented cell cycle arrest, autophagy, and cell apoptosis in the mitochondrial therapy 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.Conclusions: The study not only reveals the anti-tumor mechanism of the mitochondria but also provides a novel insight into the effect of mitochondria in different genders.