Effect of mitochondrial transcription factor A (TFAM) on aging of mouse

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1. Mitochondrial DNA nucleoid1.1. Identification of mitochondrial DNA nucleoid componentsMitochondrial nucleoids were purified by immunoprecipitation with anti-TFAM. The protein components of the nucleoids were identified by LC/MS/MS. Of the identified proteins, PDIP38 was first characterized.1.2. Protective effects of hMTH1 on oxidative damage of mitochondrial DNA and cell viabilityOver-expression of MTH1 in mice reduced oxidative damage of mitochondrial DNA induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine as well as kinate, resulting in the improvement of cell viability. These results suggest the importance of MTH1 in preventing from oxidatative damage of mitochondrial DNA caused by oxidized free guanine nucleotide.2. Effects of TEAM on aging of miceTFAM-overexpressing mice were produced. The TFAM mice showed stronger resistance to cardiac infarction than wild type mice. In addition, the TFAM mice showed much better a learning ability judged by a water maze test at 24-week old than did the same aged wild type mice. These results suggest that mitochondrial DNA is involved in the aging process and that TFAM can delay the aging process by maintaining mitochondrial DNA.