Abstract
Oscillations in chemical reactions and metabolic pathways have historiacally served as prototypes for understanding the dynamics of complex nonlinear systems. This chapter reviews the oscillatory behavior of mitochondria, with a focus on the mitochondrial oscillator dependent on reactive oxygen species (ROS), as first described in heart cells. Experimental and theoretical evidence now indicates that mitochondrial energetic variables oscillate autonomously as part of a network of coupled oscillators under both physiological and pathological conditions. The physiological domain is characterized by small-amplitude oscillations in mitochondrial membrane potential (ΔΨm) showing correlated behavior over a wide range of frequencies, as determined using Power Spectral Analysis and Relative Dispersion Analysis of long term recordings of ΔΨm. Under metabolic stress, when the balance between ROS generation and ROS scavenging is perturbed, the mitochondrial network throughout the cell locks to one main low-frequency, high-amplitude oscillatory mode. This behavior has major pathological implications because the energy dissipation and cellular redox changes that occur during ΔΨm depolarization result in suppression of electrical excitability and Ca2+ handling, the two main functions of the cardiac cell. In an ischemia/reperfusion scenario these alterations scale up to the level of the whole organ, giving rise to fatal arrhythmias.
Access provided by Autonomous University of Puebla. Download to read the full chapter text
Chapter PDF
Similar content being viewed by others
Keywords
- Reactive Oxygen Species Production
- Mitochondrial Membrane Potential
- Permeability Transition Pore
- Mitochondrial Reactive Oxygen Species
- Reactive Oxygen Species Accumulation
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
References
Strogatz SH, Sync. The Emerging Science of Spontaneous Order. New York: Hyperion Books, 2003.
Pikovsky A, Rosenblum M, Kurths J. Synchronization: A Universal Concept in Nonlinear Sciences. Vol. 29. Cambridge: Cambridge University Press, 2001.
van der Pol B, van der Mark J. The heartbeat considered as a relaxation oscillation, and an electrical model of the heart. Phil Mag 1928; 6:763–775.
Hess B, Boiteux A. Oscillatory phenomena in biochemistry. Annu Rev Biochem 1971; 40:237–258.
Rapp PE. An atlas of cellular oscillators. J Exp Biol 1979; 81:281–306.
Berridge MJ, Rapp PE. A comparative survey of the function, mechanism and control of cellular oscillators. J Exp Biol 1979; 81:217–279.
Lloyd D, Aon MA, Cortassa S. Why homeodynamics, not homeostasis? Scientific World Journal 2001; 1:133–145.
Winfree AT. The prehistory of the Belousov-Zhabotinsky oscillator. J Chem Educ 1984; 61:661–663.
Zhabotinky AM. Periodic course of the oxidation of malonic acid in a solution (Studies on the kinetics of beolusov’s reaction). Biofizika 1964; 9:306–311.
Duysens LN, Amesz J. Fluorescence spectrophotometry of reduced phosphopyridine nucleotide in intact cells in the near-ultraviolet and visible region. Biochim Biophys Acta 1957; 24(1):19–26.
Chance B, Estabrook RW, Ghosh A. Damped sinusoidal oscillations of cytoplasmic reduced pyridine nucleotide in yeast cells. Proc Natl Acad Sci USA 1964; 51:1244–1251.
Hommes FA, Schuurmansstekhoven FM. Aperiodic changes of reduced nicotinamide-adenine dinucleotide during anaerobic glycolysis in brewer’s yeast. Biochim Biophys Acta 1964; 86:427–428.
Chance B, Schoener B, Elsaesser S. Control of the waveform oscillations of the reduced pyridine nucleotide level in a cell-free extract. Proc Natl Acad Sci USA 1964: 52:337–341.
Chance B, Schoener B, Elsaesser S. Metabolic control phenomena involved in damped sinusoidal oscillations of reduced diphosphopyridine nucleotide in a cell-free extract of saccharomyces carlsbergensis. J Biol Chem 1965; 240:3170–3181.
Frenkel R. DPNH oscillations in glycolyzing cell free extracts from beef heart. Biochem Biophys Res Commun 1965; 21(5):497–502.
Frenkel R. Control of reduced diphosphopyridine nucleotide oscillations in beef heart extracts. II. Oscillations of glycolytic intermediates and adenine nucleotides. Arch Biochem Biophys 1968; 125(1):157–165.
Frenkel R. Control of reduced diphosphopyridine nucleotide oscillations in beef extracts. I. Effects of modifiers of phosphofructokinase activity. Arch Biochem Biophys 1968; 125(1):151–156.
Frenkel R. Control of reduced diphosphopyridine nucleotide oscillations in beef heart extracts. III. Purification and kinetics of beef heart phosphofructokinase. Arch Biochem Biophys 1968; 125(1):166–174.
Chance B. Federation of european biochemical societies: Biological and biochemical oscillators. New York: Academic Press 1973, (proceedings).
Lloyd D, Murray DB. The temporal architecture of eukaryotic growth. FEBS Lett 2006; 580(12):2830–2835.
Richard P. The rhythm of yeast. FEMS Microbiol Rev 2003; 27(4):547–557.
Madsen MF, Dano S, Sorensen PG. On the mechanisms of glycolytic oscillations in yeast. FEBS J 2005; 272(11):2648–2660.
Azzi A, Azzone GF. Swelling and shrinkage phenomena in liver mitochondria. II. Low amplitude swelling-shrinkage cycles. Biochim Biophys Acta 1965; 105(2):265–278.
Mustafa MG, Utsumi K, Packer L. Damped oscillatory control of mitochondrial respiration and volume. Biochem Biophys Res Commun 1966; 24(3):381–385.
Packer L, Utsumi R, Mustafa MG. Oscillatory states of mitochondria. I. Electron and energy transfer pathways. Arch Biochem Biophys 1966; 117(2):381–393.
Chance B, Yoshioka T. Sustained oscillations of ionic constituents of mitochondria. Arch Biochem Biophys 1966; 117:451–465.
Evtodienko YV. Sustained oscillations of transmembrane Ca2+ fluxes in mitochondria and their possible biological significance. Membr, Cell Biol 2000; 14:1–17.
Gylkhandanyan AV, Evtodienko YV, Zhabotinsky AM et al. Continuous Sr2+-induced oscillations of the ionic fluxes in mitochondria. FEBS Lett 1976; 66(1):44–47.
Maglova LM, Holmuhamedov EL, Zinchenko VP et al. Induction of 2H+/Me2+ exchange in rat-liver mitochondria. Eur J Biochem 1982; 128(1):159–161.
Selivanov VA, Ichas F, Holmuhamedov EL et al. A model of mitochondrial Ca(2+)-induced Ca2+ release simulating the Ca2+ oscillations and spikes generated by mitochondria. Biophys Chem 1998; 72(1–2):111–121.
Gooch VD, Packer L. Adenine nucleotide control of heart mitochondrial oscillations. Biochim Biophys Acta 1971; 245(1):17–20.
Gooch VD, Packer L. Oscillatory systems in mitochondria. Biochim Biophys Acta 1974; 346(3–4):245–260.
Gooch VD, Packer L. Oscillatory states of mitochondria: Studies on the oscillatory mechanism of liver and heart mitochondria. Arch Biochem Biophys 1974; 163(2):759–768.
O’Rourke B, Ramza BM, Marban E. Oscillations of membrane current and excitability driven by metabolic oscillations in heart cells. Science 1994; 265(5174):962–966.
Romashko DN, Marban E, O’Rourke B., Subcellular metabolic transients and mitochondrial redox waves in heart cells. Proc Natl Acad Sci USA 1998; 95(4):1618–1623.
Aon MA, Cortassa S, Marban E et al. Synchronized whole cell oscillations in mitochondrial metabolism triggered by a local release of reactive oxygen species in cardiac myocytes. J Biol Chem 2003; 278(45):44735–44744.
Kim YV, Kudzina L, Zinchenko VP et al. Clortetracyline-mediated continuous Ca2+ oscillations in mitochondria of digitonin-treated Tetrahymena pyriformis. Eur J Biochem 1985; 153(3):503–507.
Evtodienko Yu V, Teplova V, Khawaja J et al. The Ca(2+)-induced permeability transition pore is involved in Ca(2+)-induced mitochondrial oscillations: A study on permeabilised Ehrlich ascites tumour cells. Cell Calcium 1994; 15(2):143–152.
Hajnoczky G, Robb-Gaspers LD, Seitz MB et al. Decoding of cytosolic calcium oscillations in the mitochondria. Cell 1995; 82(3):415–424.
Magnus G, Keizer J. Model of beta-cell mitochondrial calcium handling and electrical activity. II. Mitochondrial variables. Am J Physiol 1998; 27(4 Pt 1):C1174–1184.
Pedersen MG, Bertram R, Sherman A. Intra-an inter-islet synchronization of metabolically driven insulin secretion. Biophys J 2005; 89(1):107–119.
Corkey BE, Tornheim K, Deeney JT et al. Linked oscillations of free Ca2+ and the ATP/ADP ratio in permeabilized RINm 5F insulinoma cells supplemented with a glycolyzing cell-free muscle extract. J Biol Chem 1988; 263(9):4254–4258.
Lloyd D. Effects of uncoupling of mitochondrial energy conservation on the ultradian clock-driven oscillations in Saccharomyces cerevisiae continuous culture. Mitochondrion 2003; 3(3): 139–136.
Mironov SL, Richter DW. Oscillations and hypoxic changes of mitochondrial variables in neurons of the brainstem respiratory centre of mice. J Physiol 2001; 533(Pt 1):227–236.
Berns MW, Siemens AE, Walter RJ. Mitochondrial fluorescence patterns in rhodamine 6G-stained myocardial cells in vitro: Analysis by real-time computer video microscopy and laser microspot excitation. Cell Biophys 1984; 6(4):263–277.
Duchen MR, Leyssens A, Crompton M. Transient mitochondrial depolarizations reflect focal sarcoplasmic reticular calcium release in single rat cardiomyocytes. J Cell Biol 1998; 142(4): 975–988.
Loew LM, Tuft RA, Carrington W et al. Imaging in five dimensions: Time-dependent membrane potentials in individual mitochondria. Biophys J 1993; 65(6): 2396–2407.
Buckman JF, Reynolds IJ. Spontaneous changes in mitochondrial membrane potential in cultured neurons. J Neurosci 2001; 21(14):5054–5065.
O’Reilly CM, Fogarty KE, Drummond RM et al. Quantitative analysis of spontaneous mitochondrial depolarizations. Biophys J 2003; 85(5):3350–3357.
O’Reilly CM, Fogarty KE, Drummond RM et al. Spontaneous mitochondrial depolarizations are independent of SR Ca2+ release. Am J Physiol Cell Physiol 2004; 286(5):C1139–1151.
Huser J, Rechenmacher, CE, Blatter LA. Imaging the permeability pore transition in single mitochondria. Biophys J 1998; 74(4):2129–2137.
Huser J, Blatter LA. Fluctuations in mitochondrial membrane potential caused by repetitive gating of the permeability transition pore. Biochem J 1999; 343(Pt 2):311–317.
Vergun O, Votyakova TV, Reynolds IJ. Spontaneous changes in mitochondrial membrane potential in single isolated brain mitochondria. Biophys J 2003; 85(5):3358–3366.
Vergun O, Reynolds IJ. Fluctuations in mitochondrial membrane potential in single isolated brain mitochondria: Modulation by adenine nucleotides and Ca2+. Biophys J 2004; 87(5):3585–3593.
Ichas F, Jouaville LS, Sidash SS et al. Mitochondrial calcium spiking: A transduction mechanism based on calcium-induced permeability transition involved in cell calcium signalling. FEBS Lett 1994; 348(2):211–215.
Zorov DB, Filburn CR, Klotz LO et al. Reactive oxygen species (ROS)-induced ROS release: A new phenomenon accompanying induction of the mitochondrial permeability transition in cardiac myocytes. J Exp Med 2000; 192(7):1001–1014.
Zorov DB, Juhaszova M, Sollott SJ. Mitochondrial ROS-induced ROS release: An update and review. Biochim Biophys Acta 2006; 1757(5–6):509–517.
O’Rourke B. Pathophysiological and protective roles of mitochondrial ion channels. J Physiol 2000; 529(Pt 1):23–36.
O’Rourke B, Ramza BM, Romashko DN et al. Metabolic oscillations in heart cells. Adv Exp Med Biol 1995; 382:165–174.
Cortassa S, Aon MA, Winslow RL et al. A mitochondrial oscillator dependent on reactive oxygen species. Biophys J 2004; 87(3):2060–2073.
Crompton M, Virji S, Doyle V et al. The mitochondrial permeability transition pore. Biochem Soc Symp 1999; 66:167–179.
Duchen MR. Contributions of mitochondria to animal physiology: From homeostatic sensor to calcium signalling and cell death. J Physiol 1999; 516 (Pt 1):1–17.
Beavis AD. On the inhibition of the mitochondrial inner membrane anion uniporter by cationic amphiphiles and other drugs. J Biol Chem 1989; 264(3):1508–1515.
Beavis AD. Properties of the inner membrane anion channel in intact mitochondria. J Bioenerg Biomembr 1992; 24(1):77–90.
Beavis AD, Garlid KD. The mitochondrial inner membrane anion channel: Regulation by divalent cations and protons. J Biol Chem 1987; 262(31):15085–15093.
Aon MA, Cortassa S, O’Rourke B. The fundamental organization of cardiac mitochondria as a network of coupled oscillators. Biophys J 2006b; 91(11):4317–4327.
Stauffer D, Aharony A. Introduction to Percolation Theory. London: Taylor and Francis, 1994.
Feder J. Fractals. New York: Plenum Press, 1988.
Aon MA, O’Rourke B, Cortassa S. The fractal architecture of cytoplasmic organization: Scaling, kinetics and emergence in metabolic networks. Mol Cell Biochem 2004b; 256/257:169–184.
Akar FG, Aon MA, Tomaselli GF et al. The mitochondrial origin of postischemic arrhythmias. J Clin Invest 2005; 115(12):3527–3535.
Bolli R, Marban E. Molecular and cellular mechanisms of myocardial stunning. Physiol Rev 1999; 79(2):609–634.
Kleber AG, Rudy Y. Basic mechanisms of cardiac impulse propagation and associated arrhythmias. Physiol Rev 2004; 84(2):431–488.
Cortassa S, Aon MA, Marban E et al. An integrated, model of cardiac mitochondrial energy metabolism and calcium dynamics. Biophys J 2003; 84(4):2734–2755.
O’Rourke B, Cortassa S, Aon MA. Mitochondrial ion channels: Gatekeepers of life and death. Physiology 2005; 20:303–315.
Aon MA, Cortassa S, Akar FG et al. Mitochondrial criticality: A new concept at the turning point of life or death. Biochim Biophys Acta 2006; 1762(2):232–240.
Aon MA, Cortassa S, O’Rourke B. Percolation and criticality in a mitochondrial network. Proc Natl Acad Sci USA 2004a; 101(13):4447–4452.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2008 Landes Bioscience and Springer Science+Business Media
About this chapter
Cite this chapter
Aon, M.A., Cortassa, S., O’Rourke, B. (2008). Mitochondrial Oscillations in Physiology and Pathophysiology. In: Maroto, M., Monk, N.A.M. (eds) Cellular Oscillatory Mechanisms. Advances in Experimental Medicine and Biology, vol 641. Springer, New York, NY. https://doi.org/10.1007/978-0-387-09794-7_8
Download citation
DOI: https://doi.org/10.1007/978-0-387-09794-7_8
Publisher Name: Springer, New York, NY
Print ISBN: 978-0-387-09793-0
Online ISBN: 978-0-387-09794-7
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)