Abstract
Mitochondrial transhydrogenase catalyzes the reaction; H +out + NADP+ + NADH = NAD+ + NADPH + H +in . The maintenance of the NADPH pool increases the mitochondrial antioxidant potential. Therefore, according to the commonly adopted free radical theory of aging, ablation of the transhydrogenase gene should reduce the life span. However, contrary to this reasoning, the life span of Caenorhabditis elegans nematodes with null mutations in the gene does not differ from that in wild-type worms. This fact indicates that free radical damage of mitochondria is not associated with aging. Meta analysis of data on the life span in mice possessing a spontaneous mutation in the transhydrogenase gene shows that a lack of this enzyme does not accelerate aging in mammals either. The heart is the tissue with the highest transhydrogenase production rate, and it is likely that this enzyme contributes to the protection of cardiac myocytes from oxidative stress.
Similar content being viewed by others
Abbreviations
- ROS:
-
reactive oxygen species
- LS:
-
life span
- FRTA:
-
free-radical theory of aging
References
Pedersen, A., Karlsson, G.B., and Rydström, J., J. Bioenerg. Biomembr., 2008, vol. 40, pp. 463–473.
Jackson, J.B., FEBS Lett., 2003, vol. 555, pp. 176–177.
Holmberg, E., Olausson, T., Hultman, T., Rydström, J., Ahmad, S., Glavas, N.A., and Bragg, P.D., Biochemistry, 1994, vol. 33, pp. 7691–7700.
Bizouarn, T., Fjellström, O., Axelsson, M., Korneenko, T.V., Pestov, N.B., Ivanova, M.V., Egorov, M.V., Shakhparonov, M.I., and Rydström, J., Eur. J. Biochem., 2000, vol. 267, pp. 3281–3288.
Hoek, J.B. and Rydström, J., Biochem. J., 1988, vol. 254, pp. 1–10.
Arkblad, E.L., Tuck, S., Pestov, N.B., Dmitriev, R.I., Kostina, M.B., Stenvall, J., Tranberg, M., and Rydström, J., Free Radic. Biol. Med., 2005, vol. 38, pp. 1518–1525.
Fujii, M., Tanaka, N., Miki, K., Hossain, M.N., Endoh, M., and Ayusawa, D., Biosci. Biotechnol. Biochem., 2005, vol. 69, pp. 2015–2018.
Freeman, H., Shimomura, K., Horner, E., Cox, R.D., and Ashcroft, F.M., Cell Metab., 2006, vol. 3, pp. 35–45.
Huang, T.T., Naeemuddin, M., Elchuri, S., Yamaguchi, M., Kozy, H.M., Carlson, E.J., and Epstein, C.J., Hum. Mol. Genet., 2006, vol. 15, pp. 1187–1194.
Arkblad, E.L., Egorov, M., Shakhparonov, M., Romanova, L., Polzikov, M., and Rydström, J., Comp. Biochem. Physiol. B. Biochem. Mol. Biol., 2002, vol. 133, pp. 13–21.
Olgun, A., Biogerontology, 2008, Oct 19. DOI 10.1007/s10522-008-9190-2.
de Magalhães, J.P., Cabral, J.A., and Magalhães, D., Genetics, 2005, vol. 169, pp. 265–274.
Howitz, K.T., Bitterman, K.J., Cohen, H.Y., Lamming, D.W., Lavu, S., Wood, J.G., Zipkin, R.E., Chung, P., Kisielewski, A., Zhang, L.L., Scherer, B., and Sinclair, D.A., Nature, 2003, vol. 425, pp. 191–196.
Bass, T.M., Weinkove, D., Houthoofd, K., Gems, D., and Partridge, L., Mech. Ageing Dev., 2007, vol. 128, pp. 546–552.
Pearson, K.J., Baur, J.A., Lewis, K.N., Peshkin, L., Price, N.L., Labinskyy, N., Swindell, W.R., Kamara, D., Minor, R.K., Perez, E., Jamieson, H.A., Zhang, Y., Dunn, S.R., Sharma, K., Pleshko, N., Woollett, L.A., Csiszar, A., and Ikeno, Y., Le Couteur D., Elliott P.J., Becker K.G., Navas P., Ingram D.K., Wolf N.S., Ungvari Z., Sinclair D.A., and De Cabo R, Cell Metab., 2008, vol. 8, pp. 157–168.
Gruber, J., Schaffer, S., and Halliwell, B., Front. Biosci., 2008, vol. 13, pp. 6554–6579.
Author information
Authors and Affiliations
Corresponding author
Additional information
Original Russian Text © N.B. Pestov, M.I. Shakhparonov, 2009, published in Bioorganicheskaya Khimiya, 2009, Vol. 35, No. 5, pp. 681–685.
Rights and permissions
About this article
Cite this article
Pestov, N.B., Shakhparonov, M.I. The effect of ablation of the gene for H+-transporting NAD/NADP transhydrogenase on the life spans of nematodes and mammals. Russ J Bioorg Chem 35, 614–618 (2009). https://doi.org/10.1134/S1068162009050124
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1134/S1068162009050124