Free radicals-mediated damage in transmitochondrial cells harboring the T14487C mutation in the ND6 gene of mtDNA.
We have studied the production of reactive oxygen species (ROS) in transmitochondrial cells, harboring homoplasmic levels of the T14487C mtDNA mutation in the ND6 gene of mitochondrial DNA (mtDNA). Previous work has shown that this mutation causes complex I deficiency. Here, we show that this mutation causes an overproduction of ROS leading to an increase in the oxidation of lipids and mtDNA without modification of antioxidant enzyme activities. We suggest that mutations in mtDNA affecting complex I activity may result in oxidative cellular damage, and reinforce the possible role of ROS-mediated mechanisms participating in some mtDNA-related disorders.
Gonzalo
Ricardo
R
Centre d'Investigacions en Bioquimica i Biologia Molecular, Hospital Vall d'Hebron, Passeig Vall d'Hebron 119-129, 08035 Barcelona, Spain.
Garcia-Arumi
Elena
E
Llige
David
D
Marti
Ramon
R
Solano
Abelardo
A
Montoya
Julio
J
Arenas
Joaquín
J
Andreu
Antonio L
AL
D004272:DNA, Mitochondrial / Q000235:genetics*; D006801:Humans; D008055:Lipids / Q000502:physiology; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism*; D009154:Mutation; D009245:NADH Dehydrogenase / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000235:genetics; D021122:Protein Subunits / Q000737:chemistry / Q000235:genetics; D017382:Reactive Oxygen Species / Q000378:metabolism*
D004272:DNA, Mitochondrial; D008055:Lipids; D021122:Protein Subunits; D017382:Reactive Oxygen Species; C507225:MT-ND6 protein, human; D009245:NADH Dehydrogenase