Abstract
The role of cardiolipin in mitochondrial energy transformation was studied by comparing oxidative phosphorylation in the Saccharomyces cerevisiae cardiolipin synthase null mutant crd1Delta, and in isogenic wild type. Oxygen consumption experiments and membrane potential kinetics during the phosphorylation cycle in isolated mitochondria indicated that the absence of cardiolipin causes only a moderate deficiency of mitochondrial energy-transforming machinery at 25 degrees C. However, at 40 degrees C, respiration was completely uncoupled from phosphorylation for the mutant mitochondria, in contrast with that for the wild-type. Membranepotential kinetics demonstrated an increased susceptibility of the mutant mitochondria to gradual deterioration during in vitro incubation. These results suggest that cardiolipin, although normally associated with several of the major enzymes of oxidative phosphorylation and required in vitro for their maximal activity, is not absolutely necessary for mitochondrial energy transformation under optimal conditions. The role of cardiolipin is, rather, to improve efficiency of oxidative phosphorylation and its resistance to unfavourable conditions, such as increased temperature.
Full Text
The Full Text of this article is available as a PDF (117.8 KB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Akerman K. E., Wikström M. K. Safranine as a probe of the mitochondrial membrane potential. FEBS Lett. 1976 Oct 1;68(2):191–197. doi: 10.1016/0014-5793(76)80434-6. [DOI] [PubMed] [Google Scholar]
- Brand M. D., Murphy M. P. Control of electron flux through the respiratory chain in mitochondria and cells. Biol Rev Camb Philos Soc. 1987 May;62(2):141–193. doi: 10.1111/j.1469-185x.1987.tb01265.x. [DOI] [PubMed] [Google Scholar]
- Brustovetsky N. N., Amerkanov Z. G., Yegorova M. E., Mokhova E. N., Skulachev V. P. Carboxyatractylate-sensitive uncoupling in liver mitochondria from ground squirrels during hibernation and arousal. FEBS Lett. 1990 Oct 15;272(1-2):190–192. doi: 10.1016/0014-5793(90)80481-w. [DOI] [PubMed] [Google Scholar]
- Brustovetsky N. N., Dedukhova V. I., Egorova M. V., Mokhova E. N., Skulachev V. P. Inhibitors of the ATP/ADP antiporter suppress stimulation of mitochondrial respiration and H+ permeability by palmitate and anionic detergents. FEBS Lett. 1990 Oct 15;272(1-2):187–189. doi: 10.1016/0014-5793(90)80480-7. [DOI] [PubMed] [Google Scholar]
- Brustovetsky N. N., Egorova M. V., Gnutov DYu, Gogvadze V. G., Mokhova E. N., Skulachev V. P. Thermoregulatory, carboxyatractylate-sensitive uncoupling in heart and skeletal muscle mitochondria of the ground squirrel correlates with the level of free fatty acids. FEBS Lett. 1992 Jun 22;305(1):15–17. doi: 10.1016/0014-5793(92)80645-w. [DOI] [PubMed] [Google Scholar]
- Castrejón V., Parra C., Moreno R., Peña A., Uribe S. Potassium collapses the deltaP in yeast mitochondria while the rate of ATP synthesis is inhibited only partially: modulation by phosphate. Arch Biochem Biophys. 1997 Oct 1;346(1):37–44. doi: 10.1006/abbi.1997.0273. [DOI] [PubMed] [Google Scholar]
- Chang S. C., Heacock P. N., Mileykovskaya E., Voelker D. R., Dowhan W. Isolation and characterization of the gene (CLS1) encoding cardiolipin synthase in Saccharomyces cerevisiae. J Biol Chem. 1998 Jun 12;273(24):14933–14941. doi: 10.1074/jbc.273.24.14933. [DOI] [PubMed] [Google Scholar]
- Dufour S., Rousse N., Canioni P., Diolez P. Top-down control analysis of temperature effect on oxidative phosphorylation. Biochem J. 1996 Mar 15;314(Pt 3):743–751. doi: 10.1042/bj3140743. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Eddy A. A. Use of carbocyanine dyes to assay membrane potential of mouse ascites tumor cells. Methods Enzymol. 1989;172:95–101. doi: 10.1016/s0076-6879(89)72010-3. [DOI] [PubMed] [Google Scholar]
- Hoch F. L. Cardiolipins and biomembrane function. Biochim Biophys Acta. 1992 Mar 26;1113(1):71–133. doi: 10.1016/0304-4157(92)90035-9. [DOI] [PubMed] [Google Scholar]
- Hoch F. L. Cardiolipins and mitochondrial proton-selective leakage. J Bioenerg Biomembr. 1998 Dec;30(6):511–532. doi: 10.1023/a:1020576315771. [DOI] [PubMed] [Google Scholar]
- Hoffmann B., Stöckl A., Schlame M., Beyer K., Klingenberg M. The reconstituted ADP/ATP carrier activity has an absolute requirement for cardiolipin as shown in cysteine mutants. J Biol Chem. 1994 Jan 21;269(3):1940–1944. [PubMed] [Google Scholar]
- Jiang F., Rizavi H. S., Greenberg M. L. Cardiolipin is not essential for the growth of Saccharomyces cerevisiae on fermentable or non-fermentable carbon sources. Mol Microbiol. 1997 Nov;26(3):481–491. doi: 10.1046/j.1365-2958.1997.5841950.x. [DOI] [PubMed] [Google Scholar]
- Laris P. C., Bahr D. P., Chaffee R. R. Membrane potentials in mitochondrial preparations as measured by means of a cyanine dye. Biochim Biophys Acta. 1975 Mar 20;376(3):415–425. doi: 10.1016/0005-2728(75)90163-2. [DOI] [PubMed] [Google Scholar]
- Lombardi A., Lanni A., Moreno M., Brand M. D., Goglia F. Effect of 3,5-di-iodo-L-thyronine on the mitochondrial energy-transduction apparatus. Biochem J. 1998 Feb 15;330(Pt 1):521–526. doi: 10.1042/bj3300521. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Manon S., Roucou X., Guérin M., Rigoulet M., Guérin B. Characterization of the yeast mitochondria unselective channel: a counterpart to the mammalian permeability transition pore? J Bioenerg Biomembr. 1998 Oct;30(5):419–429. doi: 10.1023/a:1020533928491. [DOI] [PubMed] [Google Scholar]
- Ohnishi T., Kawaguchi K., Hagihara B. Preparation and some properties of yeast mitochondria. J Biol Chem. 1966 Apr 25;241(8):1797–1806. [PubMed] [Google Scholar]
- Onishi T., Kröger A., Heldt H. W., Pfaff E., Klingenberg M. The response of the respiratory chain and adenine nucleotide system to oxidative phosphorylation in yeast mitochondria. Eur J Biochem. 1967 May;1(3):301–311. doi: 10.1007/978-3-662-25813-2_41. [DOI] [PubMed] [Google Scholar]
- Penefsky H. S. Differential effects of adenylyl imidodiphosphate on adenosine triphosphate synthesis and the partial reactions of oxidative phosphorylation. J Biol Chem. 1974 Jun 10;249(11):3579–3585. [PubMed] [Google Scholar]
- Rottenberg H., Robertson D. E., Rubin E. The effect of temperature and chronic ethanol feeding on the proton electrochemical potential and phosphate potential in rat liver mitochondria. Biochim Biophys Acta. 1985 Aug 28;809(1):1–10. doi: 10.1016/0005-2728(85)90160-4. [DOI] [PubMed] [Google Scholar]
- Roucou X., Manon S., Guérin M. Conditions allowing different states of ATP- and GDP-induced permeability in mitochondria from different strains of Saccharomyces cerevisiae. Biochim Biophys Acta. 1997 Feb 21;1324(1):120–132. doi: 10.1016/s0005-2736(96)00215-5. [DOI] [PubMed] [Google Scholar]
- Schwarz D., Kisselev P., Wessel R., Jueptner O., Schmid R. D. Alpha-branched 1,2-diacyl phosphatidylcholines as effectors of activity of cytochrome P450SCC (CYP11A1). Modeling the structure of the fatty acyl chain region of cardiolipin. J Biol Chem. 1996 May 31;271(22):12840–12846. doi: 10.1074/jbc.271.22.12840. [DOI] [PubMed] [Google Scholar]
- Shibata A., Ikawa K., Shimooka T., Terada H. Significant stabilization of the phosphatidylcholine bilayer structure by incorporation of small amounts of cardiolipin. Biochim Biophys Acta. 1994 Jun 1;1192(1):71–78. doi: 10.1016/0005-2736(94)90144-9. [DOI] [PubMed] [Google Scholar]
- Tuller G., Hrastnik C., Achleitner G., Schiefthaler U., Klein F., Daum G. YDL142c encodes cardiolipin synthase (Cls1p) and is non-essential for aerobic growth of Saccharomyces cerevisiae. FEBS Lett. 1998 Jan 2;421(1):15–18. doi: 10.1016/s0014-5793(97)01525-1. [DOI] [PubMed] [Google Scholar]
- Uribe S., Sánchez N., Peña A. Effects of K+ and other monovalent cations on yeast mitochondria. Biochem Int. 1991 Jul;24(4):615–623. [PubMed] [Google Scholar]
- Yaffe M. P. Analysis of mitochondrial function and assembly. Methods Enzymol. 1991;194:627–643. doi: 10.1016/0076-6879(91)94046-f. [DOI] [PubMed] [Google Scholar]
- Yamauchi T., Ohki K., Maruyama H., Nozawa Y. Thermal adaptation of Tetrahymena membranes with special reference to mitochondria. Role of cardiolipin in fluidity of mitochondrial membranes. Biochim Biophys Acta. 1981 Dec 7;649(2):385–392. doi: 10.1016/0005-2736(81)90428-4. [DOI] [PubMed] [Google Scholar]