Mitochondrial superoxide anion (O2·-) inducible "mev-1" animal models for aging research

  • Ishii, Takamasa (Department of Molecular Life Science, Basic Medical Science and Molecular Medicine, Tokai University School of Medicine) ;
  • Miyazawa, Masaki (Department of Molecular Life Science, Basic Medical Science and Molecular Medicine, Tokai University School of Medicine) ;
  • Hartman, Phil S. (Department of Biology, Texas Christian University) ;
  • Ishii, Naoaki (Department of Molecular Life Science, Basic Medical Science and Molecular Medicine, Tokai University School of Medicine)
  • Received : 2011.04.20
  • Published : 2011.05.31


Most intracellular reactive oxygen species (ROS), especially superoxide anion ($O_2^{{\bullet}_-}$) that is converted from oxygen, are overproduced by excessive electron leakage from the mitochondrial respiratory chain. Intracellular oxidative stress that damages cellular components can contribute to lifestyle-related diseases such as diabetes and arteriosclerosis, and age-related diseases such as cancer and neuronal degenerative diseases. We have previously demonstrated that the excessive mitochondrial $O_2^{{\bullet}_-}$ production caused by SDHC mutations (G71E in C. elegans, I71E in Drosophila and V69E in mouse) results in premature death in C. elegans and Drosophila, cancer in mouse embryonic fibroblast cells and infertility in transgenic mice. SDHC is a subunit of mitochondrial complex II. In humans, it has been reported that mutations in SDHB, SDHC or SDHD often result in inherited head and neck paragangliomas (PGLs). Recently, we established Tet-mev-1 conditional transgenic mice using our uniquely developed Tet-On/Off system, which equilibrates transgene expression to endogenous levels. These mice experienced mitochondrial respiratory chain dysfunction that resulted in $O_2^{{\bullet}_-}$ overproduction. The mitochondrial oxidative stress caused excessive apoptosis leading to low birth weight and growth retardation in the neonatal developmental phase in Tet-mev-1 mice. Here, we briefly describe the relationships between mitochondrial $O_2^{{\bullet}_-}$ and aging phenomena in mev-1 animal models


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