Possible implication of oxidative damages of mitochondria and mitochondrial DNA in the progressive renal injuries

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1. Implication of mitochondria and mitochondria injuries in the renal diseases Mitochondria produce most of the cell's energy by oxidative phosphorylation, a process that requires the coordinated actions of five respiratory enzyme complexes located in the mitochondrial inner membrane. On the other hand, emerging evidence demonstrates that mitochondria play a central role in the regulation of apoptosis. Mitochondria are regarded to be essential for cell life and death. We have delineated that oxidative modification of mitochondrial DNA accumulated and was involved in the apoptotic cell death in the process of renal diseases. We investigated the implication of mitochondrial injuries in the progressive forms of renal diseases2. Analysis of genetic background of the patients with renal diseases The mitochondrial DNA is extremely vulnerable to oxidative stress because mitochondria are the major intracellular source of ROS and have limited protection from oxidative stress. We have found increased accumulation of 8- hydroxy- 2^3- deoxyguanosine (8-OHdG), which is a product and biomarker of oxidative DNA damage, in the mitochondria of the renal tissues from patients with chronic renal disease. The hOGGl gene encodes a DNA glycosylase that excises 8- OH- Dg from damaged DNA. Genetic polymorphism of ser (S) 326Cys c has been reported. The enzymatic activity of hOGGl in the repair of 8- OH- Dg has been reported to be greater with S than with C. We found the correlation between hOGGl polymorphism and the clinical phenotype of renal diseases