Abstract
According to the ‘mitochondrial theory of aging’ it is expected that the activity of NADH Coenzyme Q reductase (Complex I) would be most severely affected among mitochondrial enzymes, since mitochondrial DNA encodes for 7 subunits of this enzyme. Being these subunits the site of binding of the acceptor substrate (Coenzyme Q) and of most inhibitors of the enzyme, it is also expected that subtle kinetic changes of quinone affinity and enzyme inhibition could develop in aging before an overall loss of activity would be observed.
The overall activity of Complex I was decreased in several tissues from aged rats, nevertheless it was found that direct assay of Complex I using artificial quinone acceptors may underevaluate the enzyme activity. The most acceptable results could be obtained by applying the ‘pool equation’ to calculate Complex I activity from aerobic NADH oxidation; using this method it was found that the decrease in Complex I activity in mitochondria from old animals was greater than the activity calculated by direct assay of NADH Coenzyme Q reductase.
A decrease of NADH oxidation and its rotenone sensitivity was observed in nonsynaptic mitochondria, but not in synaptic ‘light’ and ‘heavy’ mitochondria of brain cortex from aged rats.
In a study of Complex I activity in human platelet membranes we found that the enzyme activity was unchanged but the titre for half-inhibition by rotenone was significantly increased in aged individuals and proposed this change as a suitable biomarker of aging and age-related diseases. (Mol Cell Biochem 174: 329–333, 1997)
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Miquel J, Economos AC, Fleming JE, Johnson JE: Mitochondrial role in cell ageing. Exp Gerontol 15: 575–591, 1980
Linnane AW, Ozawa T, Marzuki S, Tanaka M: Mitochondrial DNA mutations as an important contributor to ageing and degenerative diseases. Lancet i: 642–645, 1989
Miquel J, Fleming JE: A two-step hypothesis on the mechanism of in vitro cell ageing: cellular differentiation followed by intrinsic mitochondrial mutagenesis. Exp Gerontol 19: 31–36, 1984
Tzagoloff A, Myers AM: Genetics of mitochondrial biogenesis. Ann Rev Biochem 55: 249–285, 1986
Yen TC, Su JH, King KL, Wei YH: Liver mitochondrial respiratory functions decline with age. Biochem Biophys Res Commun 178: 124–131, 1991
Cooper JM, Mann VM, Schapira AHV: Analyses of mitochondrial respiratory chain function and mitochondrial DNA deletion in human skeletal muscle: effect of ageing. J Neurol Sci 113: 91–98, 1992
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 30: 937–944, 1993
Castelluccio C, Baracca A, Fato R, Pallotti F, Maranesi M, Barzanti V, Gorini A, Villa RF, Parenti Castelli G, Marchetti M, Lenaz G: Mitochondrial activities of rat heart during ageing. Mech Ageing Dev 76: 73–88, 1994
Walker JE: The NADH:ubiquinone oxidoreductase (Complex I) of respiratory chains. Q Rev Biophys 25: 255–324, 1992
Degli Esposti M, Carelli V, Ghelli A, Crimi M, Sangiorgi S, Montagna P, Lenaz G, Lugaresi E, Cortelli P: Functional alterations of mitochondrially encoded ND-4 subunit associated with Leber’s hereditary optic neuropathy. FEBS Lett 352: 375–379, 1994
Genova ML, Castelluccio C, Fato R, Parenti Castelli G, Merlo Pich M, Formiggini G, Bovina C, Marchetti M, Lenaz G: Major changes in Complex I activity in mitochondria from aged rats may not be detected by direct assay of NADH:Coenzyme Q reductase. Biochem J 311: 105–109, 1995
Battino M, Gorini A, Villa RF, Genova ML, Bovina C, Sassi S, Littarru GP, Lenaz G: Coenzyme Q content in synaptic and nonsynaptic mitochondria from different brain regions of the ageing rat. Mech Ageing Dev 78: 173–187, 1995
Merlo Pich M, Bovina C, Formiggini G, Cometti G, Ghelli A, Genova ML, Parenti Castelli G, Marchetti M, Semeraro S, Lenaz G: Inhibitor sensitivity of respiratory Complex I in human platelets: a possible biomarker of ageing. FEBS Lett 380: 176–178, 1996
Fato R, Estornell E, Di Bernardo S, Pallotti F, Parenti Castelli G, Lenaz G: Steady-state kinetics of the reduction of Coenzyme Q analogs by Complex I in bovine heart mitochondria and submitochondrial particles. Biochemistry 35: 2705–2716, 1996
Estornell E, Fato R, Pallotti F, Lenaz G: Assay conditions for the mitochondrial NADH Coenzyme Q oxidoreductase. FEBS Lett 332: 127–131, 1993
Lenaz G, Fato R, Genova ML, Formiggini G, Parenti Castelli G, Bovina C: Underevaluation of Complex I activity by the direct assay of NADH:Coenzyme Q reductase in rat liver mitochondria. FEBS Lett 366: 119–121, 1995
Kroger A, Klingenberg M: The kinetics of redox reactions of ubiquinone related to the electron transport activity of the respiratory chain. Eur J Biochem 34: 358–368, 1973
Degli Esposti M, Ghelli A: The mechanism of proton and electron transport in mitochondrial Complex I. Biochim Biophys Acta 1187: 116–120, 1994
Paradies G, Ruggiero FM, Petrosillo G, Quagliariello E: Age-dependent decrease in the cytochrome c oxidase activity and changes in phospholipids in rat heart mitochondria. Arch Gerontol Geriatr 16: 263–272, 1993
Corral-Debrinski M, Shoffner JM, Lott MT, Wallace DC: Association of mitochondrial DNA damage with ageing and coronary atherosclerotic heart disease. Mutation Res 275: 169–180, 1992
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1997 Springer Science+Business Media Dordrecht
About this chapter
Cite this chapter
Lenaz, G. et al. (1997). Mitochondrial Complex I defects in aging. In: Gellerich, F.N., Zierz, S. (eds) Detection of Mitochondrial Diseases. Developments in Molecular and Cellular Biochemistry, vol 21. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-6111-8_50
Download citation
DOI: https://doi.org/10.1007/978-1-4615-6111-8_50
Publisher Name: Springer, Boston, MA
Print ISBN: 978-1-4613-7800-6
Online ISBN: 978-1-4615-6111-8
eBook Packages: Springer Book Archive