Abstract
We have investigated the respiratory activities and the concentrations of respiratory chain components of mitochondria isolated from the livers and hearts of two groups of rats aged 6 and 24 months respectively. In comparison with the adult controls (6 months), in aged rats there was a decline in total aerobic NADH oxidation in both tissues; only minor (non-significant) changes, however, were found in NADH:coenzyme Q reductase and cytochrome oxidase activities, and there was no change in ubiquinol-cytochrome c reductase activity. The coenzyme Q levels were slightly decreased in mitochondria from both organs of aged rats. The lowered NADH oxidase activity is not due to the slight decrease observed in the coenzyme Q levels, but is the result of decreased Complex I activity. Since the assay of NADH:coenzyme Q reductase requires quinone analogues, none of which can evoke its maximal turnover [Estornell, Fato, Pallotti and Lenaz (1993) FEBS Lett. 332, 127-131], its activity has been calculated indirectly by taking advantage of the relationship that exists between NADH oxidation and ubiquinol oxidation through the coenzyme Q pool. The results, expressed in this way, show a drastic loss of activity of Complex I in both the heart and the liver of aged animals in comparison with adult controls.
Full text
PDF![105](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2fa7/1136125/254f34f61507/biochemj00054-0107.png)
![106](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2fa7/1136125/fa706d497305/biochemj00054-0108.png)
![107](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2fa7/1136125/37b92037d4df/biochemj00054-0109.png)
![108](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2fa7/1136125/e071466ea908/biochemj00054-0110.png)
![109](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2fa7/1136125/fbe46b0dbeb1/biochemj00054-0111.png)
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Beyer R. E., Burnett B. A., Cartwright K. J., Edington D. W., Falzon M. J., Kreitman K. R., Kuhn T. W., Ramp B. J., Rhee S. Y., Rosenwasser M. J. Tissue coenzyme Q (ubiquinone) and protein concentrations over the life span of the laboratory rat. Mech Ageing Dev. 1985 Nov;32(2-3):267–281. doi: 10.1016/0047-6374(85)90085-5. [DOI] [PubMed] [Google Scholar]
- Beyer R. E. The participation of coenzyme Q in free radical production and antioxidation. Free Radic Biol Med. 1990;8(6):545–565. doi: 10.1016/0891-5849(90)90154-b. [DOI] [PubMed] [Google Scholar]
- Brown M. A., Raison J. K. The influence of storage temperature on the transition, activation enthalpy, and activity of enzymes associated with inner mitochondrial membranes. Arch Biochem Biophys. 1988 Feb 1;260(2):798–805. doi: 10.1016/0003-9861(88)90510-3. [DOI] [PubMed] [Google Scholar]
- Castelluccio C., Baracca A., Fato R., Pallotti F., Maranesi M., Barzanti V., Gorini A., Villa R. F., Parenti Castelli G., Marchetti M. Mitochondrial activities of rat heart during ageing. Mech Ageing Dev. 1994 Oct 20;76(2-3):73–88. doi: 10.1016/0047-6374(94)91583-0. [DOI] [PubMed] [Google Scholar]
- Cooper J. M., Mann V. M., Schapira A. H. Analyses of mitochondrial respiratory chain function and mitochondrial DNA deletion in human skeletal muscle: effect of ageing. J Neurol Sci. 1992 Nov;113(1):91–98. doi: 10.1016/0022-510x(92)90270-u. [DOI] [PubMed] [Google Scholar]
- Degli Esposti M., Carelli V., Ghelli A., Ratta M., Crimi M., Sangiorgi S., Montagna P., Lenaz G., Lugaresi E., Cortelli P. Functional alterations of the mitochondrially encoded ND4 subunit associated with Leber's hereditary optic neuropathy. FEBS Lett. 1994 Oct 3;352(3):375–379. doi: 10.1016/0014-5793(94)00971-6. [DOI] [PubMed] [Google Scholar]
- Degli Esposti M., Ghelli A., Crimi M., Estornell E., Fato R., Lenaz G. Complex I and complex III of mitochondria have common inhibitors acting as ubiquinone antagonists. Biochem Biophys Res Commun. 1993 Feb 15;190(3):1090–1096. doi: 10.1006/bbrc.1993.1161. [DOI] [PubMed] [Google Scholar]
- Ernster L., Forsmark-Andrée P. Ubiquinol: an endogenous antioxidant in aerobic organisms. Clin Investig. 1993;71(8 Suppl):S60–S65. doi: 10.1007/BF00226842. [DOI] [PubMed] [Google Scholar]
- Estornell E., Fato R., Castelluccio C., Cavazzoni M., Parenti Castelli G., Lenaz G. Saturation kinetics of coenzyme Q in NADH and succinate oxidation in beef heart mitochondria. FEBS Lett. 1992 Oct 19;311(2):107–109. doi: 10.1016/0014-5793(92)81378-y. [DOI] [PubMed] [Google Scholar]
- Estornell E., Fato R., Pallotti F., Lenaz G. Assay conditions for the mitochondrial NADH:coenzyme Q oxidoreductase. FEBS Lett. 1993 Oct 11;332(1-2):127–131. doi: 10.1016/0014-5793(93)80498-j. [DOI] [PubMed] [Google Scholar]
- Hansford R. G. Bioenergetics in aging. Biochim Biophys Acta. 1983 Apr 15;726(1):41–80. doi: 10.1016/0304-4173(83)90010-1. [DOI] [PubMed] [Google Scholar]
- Kalén A., Norling B., Appelkvist E. L., Dallner G. Ubiquinone biosynthesis by the microsomal fraction from rat liver. Biochim Biophys Acta. 1987 Oct 8;926(1):70–78. doi: 10.1016/0304-4165(87)90183-8. [DOI] [PubMed] [Google Scholar]
- Kröger A., Klingenberg M. The kinetics of the redox reactions of ubiquinone related to the electron-transport activity in the respiratory chain. Eur J Biochem. 1973 Apr;34(2):358–368. doi: 10.1111/j.1432-1033.1973.tb02767.x. [DOI] [PubMed] [Google Scholar]
- Kun E., Kirsten E., Piper W. N. Stabilization of mitochondrial functions with digitonin. Methods Enzymol. 1979;55:115–118. doi: 10.1016/0076-6879(79)55016-2. [DOI] [PubMed] [Google Scholar]
- Lenaz G., Fato R. Is ubiquinone diffusion rate-limiting for electron transfer? J Bioenerg Biomembr. 1986 Oct;18(5):369–401. doi: 10.1007/BF00743011. [DOI] [PubMed] [Google Scholar]
- Linnane A. W., Marzuki S., Ozawa T., Tanaka M. Mitochondrial DNA mutations as an important contributor to ageing and degenerative diseases. Lancet. 1989 Mar 25;1(8639):642–645. doi: 10.1016/s0140-6736(89)92145-4. [DOI] [PubMed] [Google Scholar]
- Majander A., Huoponen K., Savontaus M. L., Nikoskelainen E., Wikström M. Electron transfer properties of NADH:ubiquinone reductase in the ND1/3460 and the ND4/11778 mutations of the Leber hereditary optic neuroretinopathy (LHON). FEBS Lett. 1991 Nov 4;292(1-2):289–292. doi: 10.1016/0014-5793(91)80886-8. [DOI] [PubMed] [Google Scholar]
- Manzelmann M. S., Harmon H. J. Lack of age-dependent changes in rat heart mitochondria. Mech Ageing Dev. 1987 Aug;39(3):281–288. doi: 10.1016/0047-6374(87)90067-4. [DOI] [PubMed] [Google Scholar]
- Miquel J., Economos A. C., Fleming J., Johnson J. E., Jr Mitochondrial role in cell aging. Exp Gerontol. 1980;15(6):575–591. doi: 10.1016/0531-5565(80)90010-8. [DOI] [PubMed] [Google Scholar]
- Miquel J., Fleming J. E. A two-step hypothesis on the mechanisms of in vitro cell aging: cell differentiation followed by intrinsic mitochondrial mutagenesis. Exp Gerontol. 1984;19(1):31–36. doi: 10.1016/0531-5565(84)90029-9. [DOI] [PubMed] [Google Scholar]
- Müller-Höcker J. Cytochrome c oxidase deficient fibres in the limb muscle and diaphragm of man without muscular disease: an age-related alteration. J Neurol Sci. 1990 Dec;100(1-2):14–21. doi: 10.1016/0022-510x(90)90006-9. [DOI] [PubMed] [Google Scholar]
- Müller-Höcker J. Cytochrome-c-oxidase deficient cardiomyocytes in the human heart--an age-related phenomenon. A histochemical ultracytochemical study. Am J Pathol. 1989 May;134(5):1167–1173. [PMC free article] [PubMed] [Google Scholar]
- Müller-Höcker J., Schneiderbanger K., Stefani F. H., Kadenbach B. Progressive loss of cytochrome c oxidase in the human extraocular muscles in ageing--a cytochemical-immunohistochemical study. Mutat Res. 1992 Sep;275(3-6):115–124. doi: 10.1016/0921-8734(92)90016-i. [DOI] [PubMed] [Google Scholar]
- Münscher C., Rieger T., Müller-Höcker J., Kadenbach B. The point mutation of mitochondrial DNA characteristic for MERRF disease is found also in healthy people of different ages. FEBS Lett. 1993 Feb 8;317(1-2):27–30. doi: 10.1016/0014-5793(93)81484-h. [DOI] [PubMed] [Google Scholar]
- Pikó L., Hougham A. J., Bulpitt K. J. Studies of sequence heterogeneity of mitochondrial DNA from rat and mouse tissues: evidence for an increased frequency of deletions/additions with aging. Mech Ageing Dev. 1988 Jun;43(3):279–293. doi: 10.1016/0047-6374(88)90037-1. [DOI] [PubMed] [Google Scholar]
- Ragan C. I., Cottingham I. R. The kinetics of quinone pools in electron transport. Biochim Biophys Acta. 1985 Apr 8;811(1):13–31. doi: 10.1016/0304-4173(85)90003-5. [DOI] [PubMed] [Google Scholar]
- Simonetti S., Chen X., DiMauro S., Schon E. A. Accumulation of deletions in human mitochondrial DNA during normal aging: analysis by quantitative PCR. Biochim Biophys Acta. 1992 Dec 10;1180(2):113–122. doi: 10.1016/0925-4439(92)90059-v. [DOI] [PubMed] [Google Scholar]
- Sugiyama S., Hattori K., Hayakawa M., Ozawa T. Quantitative analysis of age-associated accumulation of mitochondrial DNA with deletion in human hearts. Biochem Biophys Res Commun. 1991 Oct 31;180(2):894–899. doi: 10.1016/s0006-291x(05)81149-0. [DOI] [PubMed] [Google Scholar]
- Sugiyama S., Takasawa M., Hayakawa M., Ozawa T. Changes in skeletal muscle, heart and liver mitochondrial electron transport activities in rats and dogs of various ages. Biochem Mol Biol Int. 1993 Aug;30(5):937–944. [PubMed] [Google Scholar]
- Tsai A. L., Kauten R., Palmer G. Redox changes in coenzyme Q in the millisecond time range: an approach using rapid quenching and high-performance liquid chromatography. Anal Biochem. 1985 Nov 15;151(1):131–136. doi: 10.1016/0003-2697(85)90062-4. [DOI] [PubMed] [Google Scholar]
- Tzagoloff A., Myers A. M. Genetics of mitochondrial biogenesis. Annu Rev Biochem. 1986;55:249–285. doi: 10.1146/annurev.bi.55.070186.001341. [DOI] [PubMed] [Google Scholar]
- Valls V., Castelluccio C., Fato R., Genova M. L., Bovina C., Saez G., Marchetti M., Parenti Castelli G., Lenaz G. Protective effect of exogenous coenzyme Q against damage by adriamycin in perfused rat liver. Biochem Mol Biol Int. 1994 Jul;33(4):633–642. [PubMed] [Google Scholar]
- Vanneste W. H. Molecular proportion of the fixed cytochrome components of the respiratory chain of Keilin-Hartree particles and beef heart mitochondria. Biochim Biophys Acta. 1966 Jan 11;113(1):175–178. doi: 10.1016/s0926-6593(66)80132-7. [DOI] [PubMed] [Google Scholar]
- Wolvetang E. J., Johnson K. L., Krauer K., Ralph S. J., Linnane A. W. Mitochondrial respiratory chain inhibitors induce apoptosis. FEBS Lett. 1994 Feb 14;339(1-2):40–44. doi: 10.1016/0014-5793(94)80380-3. [DOI] [PubMed] [Google Scholar]
- Yen T. C., Chen Y. S., King K. L., Yeh S. H., Wei Y. H. Liver mitochondrial respiratory functions decline with age. Biochem Biophys Res Commun. 1989 Dec 29;165(3):944–1003. doi: 10.1016/0006-291x(89)92701-0. [DOI] [PubMed] [Google Scholar]
- Yen T. C., Su J. H., King K. L., Wei Y. H. Ageing-associated 5 kb deletion in human liver mitochondrial DNA. Biochem Biophys Res Commun. 1991 Jul 15;178(1):124–131. doi: 10.1016/0006-291x(91)91788-e. [DOI] [PubMed] [Google Scholar]