Skip to main content
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1994 Dec 20;91(26):12579–12583. doi: 10.1073/pnas.91.26.12579

Physiological cytosolic Ca2+ transients evoke concurrent mitochondrial depolarizations.

L M Loew 1, W Carrington 1, R A Tuft 1, F S Fay 1
PMCID: PMC45482  PMID: 7809081

Abstract

Calcium, a ubiquitous second messenger, stimulates the activity of several mitochondrial dehydrogenases. This has led to the suggestion that the same messenger that signals cell activation could also activate mitochondrial electron/proton transport, thereby meeting demands for increased cellular energy. To test this in live cells, quantitative three-dimensional microscopy and ratio imaging were used to measure membrane potential of individual mitochondria and cytosolic calcium distribution. Mitochondria reversibly depolarized as cytosolic calcium rose and then fell following physiological stimulation. Thus, the dominant response of the mitochondrion to a rise in cytosolic [Ca2+] is to draw on the electrochemical potential, possibly to accelerate processes directly involved in ATP synthesis and calcium homeostasis.

Full text

PDF
12579

Images in this article

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bedlack R. S., Jr, Wei M., Loew L. M. Localized membrane depolarizations and localized calcium influx during electric field-guided neurite growth. Neuron. 1992 Sep;9(3):393–403. doi: 10.1016/0896-6273(92)90178-g. [DOI] [PubMed] [Google Scholar]
  2. Bolsover S. R., Spector I. Measurements of calcium transients in the soma, neurite, and growth cone of single cultured neurons. J Neurosci. 1986 Jul;6(7):1934–1940. doi: 10.1523/JNEUROSCI.06-07-01934.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. 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]
  4. Brown G. C. Control of respiration and ATP synthesis in mammalian mitochondria and cells. Biochem J. 1992 May 15;284(Pt 1):1–13. doi: 10.1042/bj2840001. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Carafoli E. Intracellular calcium homeostasis. Annu Rev Biochem. 1987;56:395–433. doi: 10.1146/annurev.bi.56.070187.002143. [DOI] [PubMed] [Google Scholar]
  6. Chacon E., Reece J. M., Nieminen A. L., Zahrebelski G., Herman B., Lemasters J. J. Distribution of electrical potential, pH, free Ca2+, and volume inside cultured adult rabbit cardiac myocytes during chemical hypoxia: a multiparameter digitized confocal microscopic study. Biophys J. 1994 Apr;66(4):942–952. doi: 10.1016/S0006-3495(94)80904-X. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Chen L. B. Mitochondrial membrane potential in living cells. Annu Rev Cell Biol. 1988;4:155–181. doi: 10.1146/annurev.cb.04.110188.001103. [DOI] [PubMed] [Google Scholar]
  8. Ehrenberg B., Montana V., Wei M. D., Wuskell J. P., Loew L. M. Membrane potential can be determined in individual cells from the nernstian distribution of cationic dyes. Biophys J. 1988 May;53(5):785–794. doi: 10.1016/S0006-3495(88)83158-8. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Farkas D. L., Wei M. D., Febbroriello P., Carson J. H., Loew L. M. Simultaneous imaging of cell and mitochondrial membrane potentials. Biophys J. 1989 Dec;56(6):1053–1069. doi: 10.1016/S0006-3495(89)82754-7. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Fein A., Tsacopoulos M. Activation of mitochondrial oxidative metabolism by calcium ions in Limulus ventral photoreceptor. Nature. 1988 Feb 4;331(6155):437–440. doi: 10.1038/331437a0. [DOI] [PubMed] [Google Scholar]
  11. Grynkiewicz G., Poenie M., Tsien R. Y. A new generation of Ca2+ indicators with greatly improved fluorescence properties. J Biol Chem. 1985 Mar 25;260(6):3440–3450. [PubMed] [Google Scholar]
  12. Gunter T. E., Pfeiffer D. R. Mechanisms by which mitochondria transport calcium. Am J Physiol. 1990 May;258(5 Pt 1):C755–C786. doi: 10.1152/ajpcell.1990.258.5.C755. [DOI] [PubMed] [Google Scholar]
  13. Hansford R. G. Relation between mitochondrial calcium transport and control of energy metabolism. Rev Physiol Biochem Pharmacol. 1985;102:1–72. doi: 10.1007/BFb0034084. [DOI] [PubMed] [Google Scholar]
  14. Harris D. A., Das A. M. Control of mitochondrial ATP synthesis in the heart. Biochem J. 1991 Dec 15;280(Pt 3):561–573. doi: 10.1042/bj2800561. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Johnson L. V., Walsh M. L., Bockus B. J., Chen L. B. Monitoring of relative mitochondrial membrane potential in living cells by fluorescence microscopy. J Cell Biol. 1981 Mar;88(3):526–535. doi: 10.1083/jcb.88.3.526. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Kimhi Y., Palfrey C., Spector I., Barak Y., Littauer U. Z. Maturation of neuroblastoma cells in the presence of dimethylsulfoxide. Proc Natl Acad Sci U S A. 1976 Feb;73(2):462–466. doi: 10.1073/pnas.73.2.462. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. 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]
  18. Loew L. M., Tuft R. A., Carrington W., Fay F. S. Imaging in five dimensions: time-dependent membrane potentials in individual mitochondria. Biophys J. 1993 Dec;65(6):2396–2407. doi: 10.1016/S0006-3495(93)81318-3. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. MITCHELL P. Coupling of phosphorylation to electron and hydrogen transfer by a chemi-osmotic type of mechanism. Nature. 1961 Jul 8;191:144–148. doi: 10.1038/191144a0. [DOI] [PubMed] [Google Scholar]
  20. McCormack J. G., Halestrap A. P., Denton R. M. Role of calcium ions in regulation of mammalian intramitochondrial metabolism. Physiol Rev. 1990 Apr;70(2):391–425. doi: 10.1152/physrev.1990.70.2.391. [DOI] [PubMed] [Google Scholar]
  21. Miyata H., Silverman H. S., Sollott S. J., Lakatta E. G., Stern M. D., Hansford R. G. Measurement of mitochondrial free Ca2+ concentration in living single rat cardiac myocytes. Am J Physiol. 1991 Oct;261(4 Pt 2):H1123–H1134. doi: 10.1152/ajpheart.1991.261.4.H1123. [DOI] [PubMed] [Google Scholar]
  22. Monck J. R., Williamson R. E., Rogulja I., Fluharty S. J., Williamson J. R. Angiotensin II effects on the cytosolic free Ca2+ concentration in N1E-115 neuroblastoma cells: kinetic properties of the Ca2+ transient measured in single fura-2-loaded cells. J Neurochem. 1990 Jan;54(1):278–287. doi: 10.1111/j.1471-4159.1990.tb13312.x. [DOI] [PubMed] [Google Scholar]
  23. Moolenaar W. H., Spector I. Membrane currents examined under voltage clamp in cultured neuroblastoma cells. Science. 1977 Apr 15;196(4287):331–333. doi: 10.1126/science.557842. [DOI] [PubMed] [Google Scholar]
  24. Moolenaar W. H., Spector I. The calcium action potential and a prolonged calcium dependent after-hyperpolarization in mouse neuroblastoma cells. J Physiol. 1979 Jul;292:297–306. doi: 10.1113/jphysiol.1979.sp012851. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Rizzuto R., Brini M., Murgia M., Pozzan T. Microdomains with high Ca2+ close to IP3-sensitive channels that are sensed by neighboring mitochondria. Science. 1993 Oct 29;262(5134):744–747. doi: 10.1126/science.8235595. [DOI] [PubMed] [Google Scholar]
  26. Rizzuto R., Simpson A. W., Brini M., Pozzan T. Rapid changes of mitochondrial Ca2+ revealed by specifically targeted recombinant aequorin. Nature. 1992 Jul 23;358(6384):325–327. doi: 10.1038/358325a0. [DOI] [PubMed] [Google Scholar]
  27. Silver R. A., Lamb A. G., Bolsover S. R. Calcium hotspots caused by L-channel clustering promote morphological changes in neuronal growth cones. Nature. 1990 Feb 22;343(6260):751–754. doi: 10.1038/343751a0. [DOI] [PubMed] [Google Scholar]
  28. Slater E. C. Mechanism of oxidative phosphorylation. Annu Rev Biochem. 1977;46:1015–1026. doi: 10.1146/annurev.bi.46.070177.005055. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Smiley S. T., Reers M., Mottola-Hartshorn C., Lin M., Chen A., Smith T. W., Steele G. D., Jr, Chen L. B. Intracellular heterogeneity in mitochondrial membrane potentials revealed by a J-aggregate-forming lipophilic cation JC-1. Proc Natl Acad Sci U S A. 1991 May 1;88(9):3671–3675. doi: 10.1073/pnas.88.9.3671. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Smith J. C., Russ P., Cooperman B. S., Chance B. Synthesis, structure determination, spectral properties, and energy-linked spectral responses of the extrinsic probe oxonol V in membranes. Biochemistry. 1976 Nov 16;15(23):5094–5105. doi: 10.1021/bi00668a023. [DOI] [PubMed] [Google Scholar]
  31. Wan B., Doumen C., Duszynski J., Salama G., Vary T. C., LaNoue K. F. Effects of cardiac work on electrical potential gradient across mitochondrial membrane in perfused rat hearts. Am J Physiol. 1993 Aug;265(2 Pt 2):H453–H460. doi: 10.1152/ajpheart.1993.265.2.H453. [DOI] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES