Abstract
N,N′-dicyclohexylcarbodiimide (DCCD) was earlier reported to have stimulatory effects on mitochondrial respiration and to induce mitochondrial swelling, when it was added to mitochondrial suspensions. These data seem to imply that DCCD caused the mitochondrial permeability transition (PT), but this possibility had never been investigated. In the present study, effects of DCCD on the mitochondrial structure and function were studied in detail. DCCD was found to induce mitochondrial PT in a cyclosporine A-insensitive manner. Electron microscopic analysis also supported the induction of the mitochondrial PT by DCCD. However, different from many other PT inducers, DCCD failed to cause massive release of mitochondrial cytochrome c. To understand the relationship between the induction of mitochondrial PT and the release of mitochondrial cytochrome c, we compared the actions of DCCD on mitochondrial structure and function with those of Ca2+, known as an ordinary PT inducer. As a result, two parameters considered to be critical for controlling the release of mitochondrial cytochrome c on the induction of PT were mitochondrial volume and the velocity of mitochondrial oxygen consumption.
Similar content being viewed by others
References
Almofti, M. R., Ichikawa, T., Yamashita, K., Terada, H., and Shinohara, Y. (2003). J. Biochem. (Tokyo) 134, 43–49.
Azzi, A., Casey, R. P., and Nalecz, M. J. (1984). Biochim. Biophys. Acta 768, 209–226.
Baines, C. P., Kaiser, R. A., Purcell, N. H., Blair, N. S., Osinska, H., Hambleton, M. A., Brunskill, E. W., Sayen, M. R., Gottlieb, R. A., Dorn, G. W., Robbins, J., and Molkentin, J. D. (2005). Nature 434, 658–662.
Basso, E., Fante, L., Fowlkes, J., Petronilli, V., Forte, M. A., and Bernardi, P. (2005). J. Biol. Chem. 280, 18558–18561.
Bauer, M. K., Schubert, A., Rocks, O., and Grimm. S. (1999). J. Cell. Biol. 147, 1493–1502.
Beatrice, M. C., Stiers, D. L., and Pfeiffer, D. R. (1982). J. Biol. Chem. 257, 7161–7171.
Bernardi, P. (1999). Physiol. Rev. 79, 1127–1155.
Bernardi, P., Petronilli, V., Di Lisa, F., and Forte, M. (2001). Trends Biochem. Sci. 26, 112–117.
Chavez, E., Zazueta, C., and Diaz, E. (1990). J. Bioenerg. Biomembr. 22, 679–689.
De Pinto, V., Al Jamal, J. A., and Palmieri, F. (1993). J. Biol. Chem. 268, 12977–12982.
De Pinto, V., Tommasino, M., Benz, R., and Palmieri, F. (1985). Biochim. Biophys. Acta 813, 230–242.
Gunter, T. E., and Pfeiffer, D. R. (1990). Am. J. Physiol. 258, C755–C786.
Hashimoto, M., Shinohara, Y., Majima, E., Hatanaka, T., Yamazaki, N., and Terada, H. (1999). Biochim. Biophys. Acta 1409, 113–124.
Jiang, D., Sullivan, P. G., Sensi, S. L., Steward, O., and Weiss, J. H. (2001). J. Biol. Chem. 276, 47524–47529.
Jung, D. W., Bradshaw, P. C., and Pfeiffer, D. R. (1997). J. Biol. Chem. 272, 21104–21112.
Kokoszka, J. E., Waymire, K. G., Levy, S. E., Sligh, J. E., Cai, J., Jones, D. P., MacGregor, G. R., and Wallace, D. C. (2004). Nature 427, 461–465.
Kroemer, G., and Reed, J. C. (2000). Nat. Med. 6, 513–519.
Li, M., Xia, T., Jiang, C. S., Li, L. J., Fu, J. L., and Zhou, Z. C. (2003). Toxicology 194, 19–33.
Li, Y., Johnson, N., Capano, M., Edwards, M., and Crompton, M. (2004). Biochem. J. 383, 101–109.
Nakagawa, T., Shimizu, S., Watanabe, T., Yamaguchi, O., Otsu, K., Yamagata, H., Inohara, H., Kubo, T., and Tsujimoto, Y. (2005). Nature 434, 652–658.
Nakashima, R. A. (1989). J. Bioenerg. Biomembr. 21, 461–470.
Nakashima, R. A., Mangan, P. S., Colombini, M., and Pedersen, P. L. (1986). Biochemistry 25, 1015–1021.
Novgorodov, S. A., Gudz, T. I., Brierley, G. P., and Pfeiffer, D. R. (1994). Arch. Biochem. Biophys. 311, 219–228.
Petronilli, V., Cola, C., Massari, S., Colonna, R., and Bernardi, P. (1993). J. Biol. Chem. 268, 21939–21945.
Pfeiffer, D. R., Gudz, T. I., Novgorodov, S. A., and Erdahl, W. L. (1995). J. Biol. Chem. 270, 4923–4932.
Scarlett, J. L., and Murphy, M. P. (1997). FEBS Lett. 418, 282–286.
Shafir, I., Feng, W., and Shoshan-Barmatz, V. (1998). Eur. J. Biochem. 253, 627–636.
Shimizu, S., Narita, M., and Tsujimoto, Y. (1999). Nature 399, 483–487.
Shinohara, Y., Almofti, M. R., Yamamoto, T., Ishida, T., Kita, F., Kanzaki, H., Ohnishi, M., Yamashita, K., Shimizu, S., and Terada, H. (2002). Eur. J. Biochem. 269, 5224–5230.
Shinohara, Y., Bandou, S., Kora, S., Kitamura, S., Inazumi, S., and Terada, H. (1998). FEBS Lett. 428, 89–92.
Sultan, A., and Sokolove, P. M. (2001). Arch. Biochem. Biophys. 386, 37–51.
Vander Heiden, M. G., and Thompson, C. B. (1999). Nature Cell Biol. 1, E209–E216.
Yamamoto, T., Tachikawa, A., Terauchi, S., Yamashita, K., Kataoka, M., Terada, H., and Shinohara, Y. (2004). Eur. J. Biochem. 271, 3573–3579.
Yamashita, K., Ichikawa, T., Yamamoto, T., Kataoka, M., Nakagawa, Y., Terada, H., and Shinohara, H. (2003). J. Health Sci. 49, 448–453.
Zamora, M., Granell, M., Mampel, T., and Vinas, O. (2004). FEBS Lett. 563, 155–160.
Zoratti, M., and Szabo, I. (1995). Biochim. Biophys. Acta 1241, 139–176.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Yamamoto, T., Terauchi, S., Tachikawa, A. et al. Two Critical Factors Affecting the Release of Mitochondrial Cytochrome c as Revealed by Studies Using N,N′-Dicyclohexylcarbodiimide as an Atypical Inducer of Permeability Transition. J Bioenerg Biomembr 37, 299–307 (2005). https://doi.org/10.1007/s10863-005-8641-6
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/s10863-005-8641-6