Abstract
A mitochondrial oscillator dependent on reactive oxygen species (ROS) was first described in heart cells. Available evidence now indicates that mitochondrial energetic variables oscillate autonomously as part of a network of coupled oscillators under both physiological and pathological conditions. Moreover, emerging experimental and theoretical evidence indicates that mitochondrial network oscillations exhibit a wide range of frequencies, from milliseconds to hours, instead of a dominant frequency. With metabolic stress, the frequency spectrum narrows and a dominant oscillatory frequency appears, indicating the transition from physiological to pathophysiological behavior.
Here we show that in the pathophysiological regime the mitochondrial oscillator of heart cells is temperature compensated within the range of 25–37°C with a Q10 = 1.13. At temperatures higher than 37°C, the oscillations stop after a few cycles, whereas at temperatures lower than 25°C the oscillations are asynchronous. Using our mitochondrial oscillator model we show that this temperature compensation can be explained by kinetic compensation. Furthermore, we show that in the physiological domain temperature compensation acts to preserve the broad range of frequencies exhibited by the network of coupled mitochondrial oscillators.
The results obtained indicate that the mitochondrial network behaves with the characteristics of a biological clock, giving rise to the intriguing hypothesis that it may function as an intracellular timekeeper across multiple time scales.
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
Anderson, R. W., Laval-Martin, D. L. and Edmunds, L. N., Jr. (1985). Cell cycle oscillators. Temperature compensation of the circadian rhythm of cell division in Euglena. Exp Cell Res 157, 144–158.
Aon, M. A., Cortassa, S., Marban, E. and O’Rourke, B. (2003). Synchronized whole cell oscillations in mitochondrial metabolism triggered by a local release of reactive oxygen species in cardiac myocytes. J Biol Chem 278, 44735–44744.
Aon, M. A., Cortassa, S. and O’Rourke, B. (2004). Percolation and criticality in a mitochondrial network. Proc Natl Acad Sci USA 101, 4447–4452.
Aon, M. A., Cortassa, S. and O’Rourke, B. (2006). The fundamental organization of cardiac mitochondria as a network of coupled oscillators. Biophys J 91, 4317–4327.
Aon, M. A., Cortassa, S. and O’Rourke, B. (2007a). On the network properties of mitochondria. Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.
Aon, M. A., Cortassa, S. and O’Rourke, B. (2007b). Mitochondrial oscillations in physiology and pathophysiology. Austin, TX: Landes Bioscience.
Balaban, R. S., Nemoto, S. and Finkel, T. (2005). Mitochondria, oxidants, and aging. Cell 120, 483–495.
Beavis, A. D. and Powers, M. (2004). Temperature dependence of the mitochondrial inner membrane anion channel: the relationship between temperature and inhibition by magnesium. J Biol Chem 279, 4045–4050.
Betz, A. and Chance, B. (1965). Influence of Inhibitors and temperature on the oscillation of reduced pyridine nucleotides in yeast cells. Arch Biochem Biophys 109, 579–584.
Cadenas, E. (2004). Mitochondrial free radical production and cell signaling. Mol Aspects Med 25, 17–26.
Casolo, G., Balli, E., Taddei, T., Amuhasi, J. and Gori, C. (1989). Decreased spontaneous heart rate variability in congestive heart failure. Am J Cardiol 64, 1162–1167.
Chance, B. and Yoshioka, T. (1966). Sustained oscillations of ionic constituents of mitochondria. Arch Biochem Biophys 117, 451–465.
Cortassa, S., Aon, M. A., Marban, E., Winslow, R. L. and O’Rourke, B. (2003). An integrated model of cardiac mitochondrial energy metabolism and calcium dynamics. Biophys J 84, 2734–2755.
Cortassa, S., Aon, M. A., Winslow, R. L. and O’Rourke, B. (2004). A mitochondrial oscillator dependent on reactive oxygen species. Biophys J 87, 2060–2073.
Droge, W. (2002). Free radicals in the physiological control of cell function. Physiol Rev 82, 47–95.
Edmunds, L. N., Jr. (1988). Cellular and molecular basis of biological clocks: models and mechanisms for circadian timekeeping. New York: Springer.
Ewing, D. J. (1991). Heart rate variability: an important new risk factor in patients following myocardial infarction. Clin Cardiol 14, 683–685.
Finkel, T. and Holbrook, N. J. (2000). Oxidants, oxidative stress and the biology of ageing. Nature 408, 239–247.
Finkel, T. (2005). Opinion: radical medicine: treating ageing to cure disease. Nat Rev Mol Cell Biol 6, 971–976.
Franck, U. F. (1980). The Teorell membrane oscillator–a complete nerve model. Ups J Med Sci 85, 265–282.
Goldberger, A. L., Bhargava, V., West, B. J. and Mandell, A. J. (1985). On a mechanism of cardiac electrical stability. The fractal hypothesis. Biophys J 48, 525–528.
Haddad, J. J. (2004). Oxygen sensing and oxidant/redox-related pathways. Biochem Biophys Res Commun 316, 969–977.
Harman, D. (1956). Aging: a theory based on free radical and radiation chemistry. J Gerontol 11, 298–300.
Harman, D. (1972). The biologic clock: the mitochondria? J Am Geriatr Soc 20, 145–147.
Kirkwood, T. (1999). Time of our lives: the science of human aging. New York: Oxford University Press.
Kirkwood, T. B. (2005). Understanding the odd science of aging. Cell 120, 437–447.
Klevecz, R. R., Bolen, J., Forrest, G. and Murray, D. B. (2004). A genome wide oscillation in transcription gates DNA replication and cell cycle. Proc Natl Acad Sci USA 101, 1200–1205.
Kuramoto, Y. (1984). Chemical oscillations, waves, and turbulence. Berlin: Springer.
Lane, N. (2002). Oxygen: the molecule that made the world. New York: Oxford University Press.
Lane, N. (2005). Power, sex, suicide: mitochondria and the meaning of life. Oxford: Oxford University Press.
Lloyd, D. (1998). Circadian and ultradian clock-controlled rhythms in unicellular microorganisms. Adv Microb Physiol 39, 291–338.
Lloyd, D. (2007). Respiratory oscillations in yeast. Austin, TX: Landes Bioscience.
Lloyd, D. and Murray, D. B. (2006). The temporal architecture of eukaryotic growth. FEBS Lett 580, 2830–2835.
Lloyd, D. and Murray, D. B. (2007). Redox rhythmicity: clocks at the core of temporal coherence. BioEssays 29, 465–473.
Lloyd, D., Aon, M. A. and Cortassa, S. (2001). Why homeodynamics, not homeostasis? ScientificWorldJournal 1, 133–145.
Mair, T., Warnke, C., Tsuji, K. and Muller, S. C. (2005). Control of glycolytic oscillations by temperature. Biophys J 88, 639–646.
Marin-Garcia, J. and Goldenthal, M. J. (2004). Heart mitochondria signaling pathways: appraisal of an emerging field. J Mol Med 82, 565–578.
Morel, Y. and Barouki, R. (1999). Repression of gene expression by oxidative stress. Biochem J 342(Pt 3), 481–496.
Murray, D. B., Roller, S., Kuriyama, H. and Lloyd, D. (2001). Clock control of ultradian respiratory oscillation found during yeast continuous culture. J Bacteriol 183, 7253–7259.
Pittendrigh, C. S. (1993). Temporal organization: reflections of a Darwinian clock-watcher. Annu Rev Physiol 55, 16–54.
Roussel, M. R. and Lloyd, D. (2007). Observation of a chaotic multioscillatory metabolic attractor by real-time monitoring of a yeast continuous culture. FEBS J 274, 1011–1018.
Ruoff, P., Christensen, M. K., Wolf, J. and Heinrich, R. (2003). Temperature dependency and temperature compensation in a model of yeast glycolytic oscillations. Biophys Chem 106, 179–192.
Skinner, J. E., Pratt, C. M. and Vybiral, T. (1993). A reduction in the correlation dimension of heartbeat intervals precedes imminent ventricular fibrillation in human subjects. Am Heart J 125, 731–743.
Strogatz, S. H. (2003). Sync: the emerging science of spontaneous order. New York: Hyperion.
Sweeney, B. M. and Hastings, J. W. (1960). Effects of temperature upon diurnal rhythms. Cold Spring Harb Symp Quant Biol 25, 87–104.
Turrens, J. F. (2003). Mitochondrial formation of reactive oxygen species. J Physiol 552, 335–344.
West, B. J. (1999). Physiology, promiscuity and prophecy at The Millennium: A tale of tails. Singapore: World Scientific.
Winfree, A. T. (1967). Biological rhythms and the behavior of populations of coupled oscillators. J Theor Biol 16, 15–42.
Wright, A. F., Jacobson, S. G., Cideciyan, A. V., Roman, A. J., Shu, X., Vlachantoni, D., McInnes, R. R. and Riemersma, R. A. (2004). Lifespan and mitochondrial control of neurodegeneration. Nat Genet 36, 1153–1158.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2008 Springer Science + Business Media B.V
About this chapter
Cite this chapter
Aon, M.A., Cortassa, S., O’Rourke, B. (2008). Is There a Mitochondrial Clock?. In: Lloyd, D., Rossi, E.L. (eds) Ultradian Rhythms from Molecules to Mind. Springer, Dordrecht. https://doi.org/10.1007/978-1-4020-8352-5_5
Download citation
DOI: https://doi.org/10.1007/978-1-4020-8352-5_5
Publisher Name: Springer, Dordrecht
Print ISBN: 978-1-4020-8351-8
Online ISBN: 978-1-4020-8352-5
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)