XXXX cell mitochondria confer apoptosis resistance and promote @entity3 .

@entity0 @entity13959 @entity5 @entity19 @entity26 @entity584 @entity2879 @entity3915 @entity3 @entity2383
Mutations in mtDNA are found in most @entity5 . In this study, we studied the role of @entity5 cell mutant mtDNA in tumorigenesis. We sequenced the entire mitochondrial genome of three different @entity0 cell lines and found that all three, MCF7, MDA-MB-231 and MDA-MB-435, contained mutations in mtDNA. MDA-MB-435 cells contained a mutation in the @entity3915 ) gene known to be involved in pathogenesis of @entity2383 . We generated a mutant cybrid (cytoplasmic hybrid) by repopulating the recipient rho(0) (completely devoid of mtDNA) cells with donor mtDNA derived from an enucleated @entity0 cell line. An isogenic wild-type cybrid was produced by transfer of normal mtDNA from a healthy donor. When compared to the wild type, we found that mutant mtDNA increases mitochondrial membrane potential. However, this increase in mitochondrial membrane potential was not associated with increase in reactive @entity26 species (ROS) production. MtDNA mutations conferred resistance to apoptosis triggered by @entity2879 . Our study also revealed that mutations in mtDNA increase metastatic potential. Using a tail-vein model of @entity3 in a @entity19 model, we show that the mutant cybrid metastatizes to the lungs and forms macrometastic foci. Additionally we found that mutations in mtDNA constitutively activate the @entity13959 / @entity584 pathway that contributes to increased metastatis. Together our study demonstrates that mutant mtDNA promotes apoptotic resistance and @entity3 in a @entity19 model.
