The single subunit NADH dehydrogenase reduces generation of reactive oxygen species from complex I.
Using rat dopaminergic and human neuroblastoma cell lines transduced with the NDI1 gene encoding the internal NADH dehydrogenase (Ndi1) from Saccharomyces cerevisiae, we investigated reactive oxygen species (ROS) generation caused by complex I inhibition. Incubation of non-transduced cells with rotenone elicited oxidative damage to mitochondrial DNA as well as lipid peroxidation. In contrast, oxidative stress was significantly decreased when the cells were transduced with NDI1. Furthermore, mitochondria from the NDI1-transduced cells showed a suppressed rate of ROS formation by the complex I inhibitors. We conclude that the Ndi1 enzyme is able to suppress ROS overproduction from defective complex I.
Seo
Byoung Boo
BB
Division of Biochemistry, Department of Molecular and Experimental Medicine, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
Marella
Mathieu
M
Yagi
Takao
T
Matsuno-Yagi
Akemi
A
D000818:Animals; D002460:Cell Line; D004249:DNA Damage / Q000187:drug effects; D004272:DNA, Mitochondrial; D042967:Electron Transport Complex I / Q000037:antagonists & inhibitors / Q000378:metabolism*; D006801:Humans; D015227:Lipid Peroxidation / Q000187:drug effects; D009245:NADH Dehydrogenase / Q000502:physiology*; D018384:Oxidative Stress; D021122:Protein Subunits; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D012402:Rotenone / Q000494:pharmacology; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics; D014161:Transduction, Genetic
D004272:DNA, Mitochondrial; D021122:Protein Subunits; D017382:Reactive Oxygen Species; D029701:Saccharomyces cerevisiae Proteins; D012402:Rotenone; D009245:NADH Dehydrogenase; D042967:Electron Transport Complex I