Since the mutagenesis of mitochondrial genome in mammals is not possible yet, we have exploited budding yeast S. cerevisiae as a model to study the effects of tumor-associated mutations in the mitochondrial MTATP6 gene, encoding subunit 6 of ATP synthase, on the energy metabolism.
In regard to the molecular study, after sequencing the coding region of ATP6 and ND3 genes of the DNA obtained from both leukocytes and tumor tissue, we did not find somatic mutations.
We observed differential expression of mitochondrial 12S/MT-RNR1, MT-CO2/COX2, and MT-ATP6 transcripts in tumor samples when compared to their paired normal samples.
To determine whether mutant tumors had increased ROS and tumor growth rates, we introduced the pathogenic mtDNA ATP6T8993G mutation into the PC3 prostate cancer cell line through cybrid transfer and tested for tumor growth in nude mice.