Skip to main content
NCBI home page
Biochemical Journal logoLink to Biochemical Journal
. 1983 Jul 15;214(1):163–170. doi: 10.1042/bj2140163

Mitochondrial Ca2+ transport in lean and genetically obese (ob/ob) mice.

D R Fraser, P Trayhurn
PMCID: PMC1152221  PMID: 6615461

Abstract

Isolated mitochondria from liver or brown adipose tissue of obese ob/ob mice demonstrated increased rates of Ca2+ uptake and release compared with those of lean mice. This enhanced transport activity was not found in mitochondria from kidney or skeletal muscle. Respiration-induced membrane potential was the same in mitochondria from lean and ob/ob mice. It is therefore concluded that the increased Ca2+ uptake rates reflect an activation of the Ca2+ uniporter rather than a change in the electrophoretic driving force. As mitochondria from pre-obese ob/ob mice did not show elevated rates of Ca2+ transport, the activated transport in the obese animals was thus a consequence of the state of obesity rather than being a direct effect of the ob/ob genotype. It is suggested that the enhanced activity of the Ca2+-transport pathways in liver and brown adipose tissue may alter metabolic functions in these tissues by modifying cytoplasmic or intramitochondrial Ca2+ concentrations.

Full text

PDF
163

Selected References

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

  1. Al-Shaikhaly M. H., Nedergaard J., Cannon B. Sodium-induced calcium release from mitochondria in brown adipose tissue. Proc Natl Acad Sci U S A. 1979 May;76(5):2350–2353. doi: 10.1073/pnas.76.5.2350. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bray G. A., York D. A. Hypothalamic and genetic obesity in experimental animals: an autonomic and endocrine hypothesis. Physiol Rev. 1979 Jul;59(3):719–809. doi: 10.1152/physrev.1979.59.3.719. [DOI] [PubMed] [Google Scholar]
  3. Bygrave F. L. Mitochondria and the control of intracellular calcium. Biol Rev Camb Philos Soc. 1978 Feb;53(1):43–79. doi: 10.1111/j.1469-185x.1978.tb00992.x. [DOI] [PubMed] [Google Scholar]
  4. Cannon B., Lindberg O. Mitochondria from brown adipose tissue: isolation and properties. Methods Enzymol. 1979;55:65–78. doi: 10.1016/0076-6879(79)55010-1. [DOI] [PubMed] [Google Scholar]
  5. Cheah K. S., Cheah A. M. Mitochondrial calcium transport and calcium-activated phospholipase in porcine malignant hyperthermia. Biochim Biophys Acta. 1981 Jan 14;634(1):70–84. doi: 10.1016/0005-2728(81)90128-6. [DOI] [PubMed] [Google Scholar]
  6. Crompton M., Heid I. The cycling of calcium, sodium, and protons across the inner membrane of cardiac mitochondria. Eur J Biochem. 1978 Nov 15;91(2):599–608. doi: 10.1111/j.1432-1033.1978.tb12713.x. [DOI] [PubMed] [Google Scholar]
  7. Crompton M., Moser R., Lüdi H., Carafoli E. The interrelations between the transport of sodium and calcium in mitochondria of various mammalian tissues. Eur J Biochem. 1978 Jan 2;82(1):25–31. doi: 10.1111/j.1432-1033.1978.tb11993.x. [DOI] [PubMed] [Google Scholar]
  8. Denton R. M., McCormack J. G. On the role of the calcium transport cycle in heart and other mammalian mitochondria. FEBS Lett. 1980 Sep 22;119(1):1–8. doi: 10.1016/0014-5793(80)80986-0. [DOI] [PubMed] [Google Scholar]
  9. Dorman D. M., Barritt G. J., Bygrave F. L. Stimulation of hepatic mitochondrial calcium transport by elevated plasma insulin concentrations. Biochem J. 1975 Sep;150(3):389–395. doi: 10.1042/bj1500389. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Edwards M. W., Cawthorne M. A., Williamson D. H. Impairment of effects of vasopressin on [1-14C]oleate metabolism in hepatocytes from obese (ob/ob) mice. Biochem J. 1981 Jul 15;198(1):239–242. doi: 10.1042/bj1980239. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Fiskum G., Lehninger A. L. Regulated release of Ca2+ from respiring mitochondria by Ca2+/2H+ antiport. J Biol Chem. 1979 Jul 25;254(14):6236–6239. [PubMed] [Google Scholar]
  12. Goodbody A. E., Trayhurn P. GDP binding to brown-adipose-tissue mitochondria of diabetic--obese (db/db) mice. Decreased binding in both the obese and pre-obese states. Biochem J. 1981 Mar 15;194(3):1019–1022. doi: 10.1042/bj1941019. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Greenway D. C., Himms-Hagen J. Increased calcium uptake by muscle mitochondria of cold-acclimated rats. Am J Physiol. 1978 Jan;234(1):C7–13. doi: 10.1152/ajpcell.1978.234.1.C7. [DOI] [PubMed] [Google Scholar]
  14. Grist E. M., Baum H. Evidence for a halothane-dependent cyclic flux of calcium in rat-liver mitochondria. Eur J Biochem. 1975 Sep 15;57(2):617–620. doi: 10.1111/j.1432-1033.1975.tb02337.x. [DOI] [PubMed] [Google Scholar]
  15. Halestrap A. P. Stimulation of pyruvate transport in metabolizing mitochondria through changes in the transmembrane pH gradient induced by glucagon treatment of rats. Biochem J. 1978 Jun 15;172(3):389–398. doi: 10.1042/bj1720389. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Heaton G. M., Nicholls D. G. The calcium conductance of the inner membrane of rat liver mitochondria and the determination of the calcium electrochemical gradient. Biochem J. 1976 Jun 15;156(3):635–646. doi: 10.1042/bj1560635. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Himms-Hagen J., Desautels M. A mitochondrial defect in brown adipose tissue of the obese (ob/ob) mouse: reduced binding of purine nucleotides and a failure to respond to cold by an increase in binding. Biochem Biophys Res Commun. 1978 Jul 28;83(2):628–634. doi: 10.1016/0006-291x(78)91036-7. [DOI] [PubMed] [Google Scholar]
  18. Hogan S., Himms-Hagen J. Abnormal brown adipose tissue in obese (ob/ob) mice: response to acclimation to cold. Am J Physiol. 1980 Oct;239(4):E301–E309. doi: 10.1152/ajpendo.1980.239.4.E301. [DOI] [PubMed] [Google Scholar]
  19. Kawashima H., Castro A. Effect of 1 alpha-hydroxyvitamin D3 on the glucose and calcium metabolism in genetic obese mice. Res Commun Chem Pathol Pharmacol. 1981 Jul;33(1):155–161. [PubMed] [Google Scholar]
  20. Kessar P., Crompton M. The alpha-adrenergic-mediated activation of Ca2+ influx into cardiac mitochondria. A possible mechanism for the regulation of intramitochondrial free CA2+. Biochem J. 1981 Nov 15;200(2):379–388. doi: 10.1042/bj2000379. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Kimura S., Rasmussen H. Adrenal glucocorticoids, adenine nucleotide translocation, and mitochondrial calcium accumulation. J Biol Chem. 1977 Feb 25;252(4):1217–1225. [PubMed] [Google Scholar]
  22. Lötscher H. R., Winterhalter K. H., Carafoli E., Richter C. The energy-state of mitochondria during the transport of Ca2+. Eur J Biochem. 1980 Sep;110(1):211–216. doi: 10.1111/j.1432-1033.1980.tb04857.x. [DOI] [PubMed] [Google Scholar]
  23. Makinen M. W., Lee C. P. Biochemical studies of skeletal muscle mitochondria. I. Microanalysis of cytochrome content, oxidative and phosphorylative activities of mammalian skeletal muscle mitochondria. Arch Biochem Biophys. 1968 Jul;126(1):75–82. doi: 10.1016/0003-9861(68)90561-4. [DOI] [PubMed] [Google Scholar]
  24. Murphy E., Coll K., Rich T. L., Williamson J. R. Hormonal effects on calcium homeostasis in isolated hepatocytes. J Biol Chem. 1980 Jul 25;255(14):6600–6608. [PubMed] [Google Scholar]
  25. Nicholls D. G., Brand M. D. The nature of the calcium ion efflux induced in rat liver mitochondria by the oxidation of endogenous nicotinamide nucleotides. Biochem J. 1980 Apr 15;188(1):113–118. doi: 10.1042/bj1880113. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Nicholls D. G. Brown adipose tissue mitochondria. Biochim Biophys Acta. 1979 Jul 3;549(1):1–29. doi: 10.1016/0304-4173(79)90016-8. [DOI] [PubMed] [Google Scholar]
  27. Nicholls D. G. The influence of respiration and ATP hydrolysis on the proton-electrochemical gradient across the inner membrane of rat-liver mitochondria as determined by ion distribution. Eur J Biochem. 1974 Dec 16;50(1):305–315. doi: 10.1111/j.1432-1033.1974.tb03899.x. [DOI] [PubMed] [Google Scholar]
  28. Nicholls D. G. The regulation of extramitochondrial free calcium ion concentration by rat liver mitochondria. Biochem J. 1978 Nov 15;176(2):463–474. doi: 10.1042/bj1760463. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Puskin J. S., Gunter T. E., Gunter K. K., Russell P. R. Evidence for more than one Ca2+ transport mechanism in mitochondria. Biochemistry. 1976 Aug 24;15(17):3834–3842. doi: 10.1021/bi00662a029. [DOI] [PubMed] [Google Scholar]
  30. ROSSI C. S., LEHNINGER A. L. STOICHIOMETRY OF RESPIRATORY STIMULATION, ACCUMULATION OF CA++ AND PHOSPHATE, AND OXIDATIVE PHOSPHORYLATION IN RAT LIVER MITOCHONDRIA. J Biol Chem. 1964 Nov;239:3971–3980. [PubMed] [Google Scholar]
  31. Reed K. C., Bygrave F. L. Methodology for in vitro studies of Ca-2+ transport. Anal Biochem. 1975 Jul;67(1):44–54. doi: 10.1016/0003-2697(75)90270-5. [DOI] [PubMed] [Google Scholar]
  32. Scott I. D., Nicholls D. G. Energy transduction in intact synaptosomes. Influence of plasma-membrane depolarization on the respiration and membrane potential of internal mitochondria determined in situ. Biochem J. 1980 Jan 15;186(1):21–33. doi: 10.1042/bj1860021. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Seitz H. J., Krone W., Wilke H., Tarnowski W. Rapid rise in plasma glucagon induced by acute cold exposure in man and rat. Pflugers Arch. 1981 Jan;389(2):115–120. doi: 10.1007/BF00582100. [DOI] [PubMed] [Google Scholar]
  34. Siegel E. G., Wollheim C. B., Sharp G. W., Herberg L., Renold A. E. Role of Ca2+ in impaired insulin release from islets of diabetic (C57BL/KsJ-db/db) mice. Am J Physiol. 1980 Aug;239(2):E132–E138. doi: 10.1152/ajpendo.1980.239.2.E132. [DOI] [PubMed] [Google Scholar]
  35. Stucki J. W., Ineichen E. A. Energy dissipation by calcium recycling and the efficiency of calcium transport in rat-liver mitochondria. Eur J Biochem. 1974 Oct 2;48(2):365–375. doi: 10.1111/j.1432-1033.1974.tb03778.x. [DOI] [PubMed] [Google Scholar]
  36. Taylor W. M., Prpić V., Exton J. H., Bygrave F. L. Stable changes to calcium fluxes in mitochondria isolated from rat livers perfused with alpha-adrenergic agonists and with glucagon. Biochem J. 1980 May 15;188(2):443–450. doi: 10.1042/bj1880443. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Thurlby P. L., Trayhurn P. Regional blood flow in genetically obese (ob/ob) mice. The importance of brown adipose tissue to the reduced energy expenditure on non-shivering thermogenesis. Pflugers Arch. 1980 Jun;385(3):193–201. doi: 10.1007/BF00647457. [DOI] [PubMed] [Google Scholar]
  38. Trayhurn P. Fatty acid synthesis in brown adipose tissue in relation to whole body synthesis in the cold-acclimated golden hamster (Mesocricetus auratus). Biochim Biophys Acta. 1980 Oct 6;620(1):10–17. doi: 10.1016/0005-2760(80)90179-4. [DOI] [PubMed] [Google Scholar]
  39. Trayhurn P., James W. P. Thermoregulation and non-shivering thermogenesis in the genetically obese (ob/ob) mouse. Pflugers Arch. 1978 Feb 22;373(2):189–193. doi: 10.1007/BF00584859. [DOI] [PubMed] [Google Scholar]
  40. Trayhurn P., Thurlby P. L., James W. P. Thermogenic defect in pre-obese ob/ob mice. Nature. 1977 Mar 3;266(5597):60–62. doi: 10.1038/266060a0. [DOI] [PubMed] [Google Scholar]
  41. Zoccarato F., Nicholls D. The role of phosphate in the regulation of the independent calcium-efflux pathway of liver mitochondria. Eur J Biochem. 1982 Oct;127(2):333–338. doi: 10.1111/j.1432-1033.1982.tb06875.x. [DOI] [PubMed] [Google Scholar]

Articles from Biochemical Journal are provided here courtesy of The Biochemical Society

RESOURCES