Role of ectopically expressed mtDNA encoded cytochrome c oxidase subunit I (MT-COI) in tumorigenesis

Publication date: Available online 9 July 2019Source: MitochondrionAuthor(s): Rajnish Kumar Singh, Sunil Kumar Saini, Gopinath Prakasam, Ponnuusamy Kalairasan, Rameshwar N.K. BamezaiAbstractSomatic mutations within mitochondrial DNA (mtDNA) encoded cytochrome c oxidase subunit I (MT-COI) are frequent in various cancer types. In addition, perturbation from orchestrated expression of mitochondrial DNA encoded genes is also associated with complex disorders, including cancer. Since codon bias and the mitochondrial translation system restricts functional characterization of over-expressed wild type or mutant mitochondrial DNA encoded genes, the codon optimization and artificial synthesis of entire MT-CO1 allowed us to over-express the wild type and one of its deleterious mutants into the mitochondria of the transfected cells. Ectopically expressed MT-CO1 was observed to efficiently expressed and localized to mitochondria but showed high level of aggregation under denaturing condition upon heating. Over-expression of wild type or mutant variant of MT-CO1 promoted anchorage dependent and independent proliferation potential in in-vitro experiments and introduced the cancer cell metabolic phenotype of high glucose uptake and lactate release. Reactive oxygen species generated in cells over-expressing MT-CO1 variants acted as key effectors mediating differential expression of apoptosis and DNA damage pathway related genes. High ROS generated also down-regulated the expression of global...

Source: Mitochondrion - July 10, 2019 Category: Biochemistry Source Type: research