Investigating interspecies mitochondrial transplantation on the malignancy of melanoma cells

Transplanting allogeneic or even interspecies mitochondria to modulate cancer malignancy was investigated herein. Melanoma is a highly metastatic cancer that strongly relies on mitochondrial function. The mitochondrial membrane potential (MMP) and ATP of human (A375) and mouse (B16F10) melanoma cells, and four donor cells, human and mouse (MPEK-BL6) keratinocytes, human (HUVEC) and mouse endothelial cells were compared. The mitochondrial transplantations between mouse and human were identified. HUVEC mitochondria could uniquely retard the migration of B16F10. HUVEC mitochondria could be substantially transplanted into B16F10 and were colocalized with endogenous B16F10 mitochondria, in which, the branched mitochondria were converted into globular mitochondria. The reduced DRP1 and LC3 II corresponded to the reduced MMP and ATP. The decreased TGF-β, NANOG, SOX2, SMAD2/3, AKT, ERK, N-cadherin, and MMP-9 corresponded to the attenuated invasion, elevated reactive oxygen species and impaired cell viability. In conclusion, the feasibility of interspecies mitochondrial transplantation was preliminarily validated.