M.V. Berridge, A.S. Tan

Mammalian cells contain multiple mitochondria with each mitochondrion containing several genomes. With few known exceptions, mitochondria are retained within their cell of origin. Nevertheless, intercellular mitochondrial transfer via membrane nanotubes has been demonstrated in cell culture systems in vitro and recent phylogenetic evidence has indicated that mitochondrial gene transfer from host to tumour cells occurs in a canine transmissible venereal tumour (Rebbeck et. al., Science 331: 303 2011). Intercellular mitochondrial gene transfer has not been demonstrated physiologically. Here, we present evidence that metastatic 4T1 breast carcinoma cells and B16 melanoma cells that lack a mitochondrial genome and respiratory function acquire a mitochondrial gene marker and respiratory function following injection into recipient mice. This mitochondrial genome acquisition triggers tumorigenesis after a 20-30 day lag period and subsequent metastasis to the lung in both models. Transformed cells exhibit stable properties indistinguishable from those of parental cells. The most likely explanation for these results is horizontal transfer of mitochondrial genes from the tumour microenvironment to the mitochondrial genome-knockout tumour cells by a mechanism involving membrane nanotube-mediated movement of mitochondria between cells. Intercellular mitochondrial transfer may be relevant not only to glycolytic cancers with mitochondrial genome damage, but also in other diseases involving mitochondrial dysfunction and in ageing.

Keywords (Optional): 
mitochondrial genome
cell metabolism
horizontal gene transfer