Oxidative stress, mtDNA mutation

Lewis W, Levine ES, Griniuviene B, Tankersley KO, Colacino JM, Sommadossi JP, Watanabe KA, Perrino FW (1996b) Fialiuidine and its metabolites inhibit DNA polymerase y at sites of multiple adjacent analog incorporation, decrease mtDNA abundance, and cause mitochraidrial structural defects in cultiued hepatoblasts. Proc Natl Acad Sd USA 93 3592-3597 Lewis W, Copeland WC, Day BJ (2001) Mitochondrial DNA depletion, oxidative stress and mutation mechanisms of dysfunction from nucleoside reverse transcriptase inhihitors. Lab Invest 81 777-790... 

Oxidative Stress and Oxidative Damage Elicited by mtDNA Mutations. 102... 

On the other hand, defective respiratory function elicited by the mtDNA mutation contributes to an increase in the production of ROS and free radicals, thereby causing higher oxidative stress and severe oxidative damage in affected cells (P2, W6). Because either enhanced oxidative stress or disruption of calcium homeostasis is an important factor in the triggering of cell death, mitochondrial dysfunction in tissue cells from MELAS and MERRF patients may contribute significantly to the pathogenesis of these diseases. 

W9. Wong, A., and Cortopassi, G., mtDNA mutations confer cellular sensitivity to oxidant stress that is partially rescued by calcium depletion and cyclosporin A. Biochem. Biophys. Res. Commun. 239, 139-145 (1997). 

Institute, Lisbon, Portugal) in the August/September 2006 Townsend Letter for Doctors Patients. (Mitochondria are the subcellular organelles that produce cellular energy via the formation of ATP, or adenosine triphosphate.) The article speaks of breaks in the mitochondrial DNA (MTDNA) traceable to oxidative stress from free radicals and possibly to chemotherapy itself, which can lead to cellular defects, mutations, and cancer. The formation and renewal of MTDNA involves the enzyme mitochondrial polymerase (and the inhibition of this enzyme can be viewed as one more factor in this complex scenario). 

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