Mitochondrial ND5 mutation mediated elevated ROS regulates apoptotic pathway epigenetically in a P53 dependent manner for generating pro-cancerous phenotypes

Mitochondrion
Rajnish Kumar SinghRameshwar N K Bamezai

Abstract

We have previously observed concomitant events of mutations in mitochondrial and nuclear genes, along with elevated reactive oxygen species (ROS) and differential methylation within the promoters of nuclear genes in tumors and in vitro experiments of tumorigenesis. These observations have made it pertinent to replicate and understand the role of acquired mitochondrial condition in tuning a cell to accomplish a pro-cancerous state. Using a codon optimized vector system for exogenous over-expression and mitochondrial localization; we have characterized here the role of over-expressed wild type mtND5 and one of its non-synonymous somatic mutation, ND5:P265H. The ectopically over-expressed ND5:P265H in mitochondria resulted in a reduced Complex I activity, generation of higher ADP/ATP ratio, reactive oxygen species (ROS) and carbonylation of proteins as compared to mock-transfected cells. Cells over-expressing mtND5 variant produced both peroxide as well as super-oxide ROS; the generation of which was dependent on the functional status of P53; modulating epigenetically the expression of key apoptosis pathway genes. The pro-cancerous phenotypes, of anchorage dependent and independent growth; increased glucose uptake and lactate prod...Continue Reading

Citations

Jan 17, 2020·DNA and Cell Biology·Ngoc Ngo Yen NguyenYong Hwa Jo
Jun 25, 2020·International Journal of Molecular Sciences·Jean NakhleMarie-Luce Vignais
Aug 14, 2020·Journal of Cellular Biochemistry·Yingzhou ShiYueliang Shen
Jul 13, 2019·Mitochondrion·Rajnish Kumar SinghRameshwar N K Bamezai

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