Abstract
Rat liver mitochondria were incubated in media of different osmolarities and in the presence of various substrates. Rates of oxygen consumption and mitochondrial matrix volumes were measured in the presence and absence of ADP and uncoupler. Duroquinol oxidation was insensitive to matrix volume, whereas other substrates tested showed increased rates of oxidation when the matrix volume increased from 1.0 to 1.5 microliter/mg of protein; this is the range of values measured in situ [Quinlan, Thomas, Armston & Halestrap (1983) Biochem. J. 214, 395-404]. Palmitoylcarnitine, octanoate and butyrate oxidations were particularly sensitive to the matrix volume, increasing from negligible rates to maximal rates within this range. Swelling induced by K+ uptake also stimulated palmitoylcarnitine oxidation. A similar effect of volume on substrate oxidation was seen when ferricyanide in the presence or absence of ubiquinone-1 replaced oxygen as terminal electron acceptor. Measurement of flavoprotein reduction (A 460-480) demonstrated that the locus of the effect of matrix volume is between the electron-transfer flavoprotein and ubiquinone. It is suggested that volume-mediated regulation of fatty acid and proline oxidation may be an important component of the hormonal stimulation of their oxidation.
Full text
PDF






Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Armston A. E., Halestrap A. P., Scott R. D. The nature of the changes in liver mitochondrial function induced by glucagon treatment of rats. The effects of intramitochondrial volume, aging and benzyl alcohol. Biochim Biophys Acta. 1982 Sep 15;681(3):429–439. doi: 10.1016/0005-2728(82)90185-2. [DOI] [PubMed] [Google Scholar]
- Assimacopoulos-Jeannet F., Denton R. M., Jeanrenaud B. Stimulation of hepatic lipogenesis and acetyl-coenzyme A carboxylase by vasopressin. Biochem J. 1981 Sep 15;198(3):485–490. doi: 10.1042/bj1980485. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bookelman H., Trijbels J. M., Sengers R. C., Janssen A. J., Veerkamp J. H., Stadhouders A. M. The effect of exogenous cytochrome c on pyruvate oxidation by rat skeletal muscle mitochondria isolated in sucrose or KCI medium. Biochem Med. 1978 Dec;20(3):404–416. doi: 10.1016/0006-2944(78)90090-x. [DOI] [PubMed] [Google Scholar]
- Brocks D. G., Siess E. A., Wieland O. H. Distinctive roles of oleate and glucagen in gluconeogenesis. Eur J Biochem. 1980 Dec;113(1):39–43. doi: 10.1111/j.1432-1033.1980.tb06136.x. [DOI] [PubMed] [Google Scholar]
- CRANE F. L., BEINERT H. On the mechanism of dehydrogenation of fatty acyl derivatives of coenzyme A. II. The electron-transferring flavoprotein. J Biol Chem. 1956 Feb;218(2):717–731. [PubMed] [Google Scholar]
- Chisholm A. B., Allan E. H., Titheradge M. A. Regulation of mitochondrial pyruvate carboxylation in isolated hepatocytes by acute insulin treatment. Biochem J. 1983 Aug 15;214(2):451–458. doi: 10.1042/bj2140451. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Christiansen R. Z. Regulation of palmitate metabolism by carnitine and glucagon in hepatocytes isolated from fasted and carbohydrate refed rats. Biochim Biophys Acta. 1977 Aug 24;488(2):249–262. doi: 10.1016/0005-2760(77)90182-5. [DOI] [PubMed] [Google Scholar]
- Denton R. M., McCormack J. G. Ca2+ transport by mammalian mitochondria and its role in hormone action. Am J Physiol. 1985 Dec;249(6 Pt 1):E543–E554. doi: 10.1152/ajpendo.1985.249.6.E543. [DOI] [PubMed] [Google Scholar]
- Halestrap A. P., Quinlan P. T., Armston A. E., Whipps D. E. Mechanisms involved in hormone signal transduction across the mitochondrial membrane. Biochem Soc Trans. 1985 Aug;13(4):659–663. doi: 10.1042/bst0130659. [DOI] [PubMed] [Google Scholar]
- Halestrap A. P., Quinlan P. T. The intramitochondrial volume measured using sucrose as an extramitochondrial marker overestimates the true matrix volume determined with mannitol. Biochem J. 1983 Aug 15;214(2):387–393. doi: 10.1042/bj2140387. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Halestrap A. P., Quinlan P. T., Whipps D. E., Armston A. E. Regulation of the mitochondrial matrix volume in vivo and in vitro. The role of calcium. Biochem J. 1986 Jun 15;236(3):779–787. doi: 10.1042/bj2360779. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Halestrap A. P. The mitochondrial pyruvate carrier. Kinetics and specificity for substrates and inhibitors. Biochem J. 1975 Apr;148(1):85–96. doi: 10.1042/bj1480085. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Halestrap A. P. The nature of the stimulation of the respiratory chain of rat liver mitochondria by glucagon pretreatment of animals. Biochem J. 1982 Apr 15;204(1):37–47. doi: 10.1042/bj2040037. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Häussinger D., Sies H. Effect of phenylephrine on glutamate and glutamine metabolism in isolated perfused rat liver. Biochem J. 1984 Aug 1;221(3):651–658. doi: 10.1042/bj2210651. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ikeda Y., Okamura-Ikeda K., Tanaka K. Purification and characterization of short-chain, medium-chain, and long-chain acyl-CoA dehydrogenases from rat liver mitochondria. Isolation of the holo- and apoenzymes and conversion of the apoenzyme to the holoenzyme. J Biol Chem. 1985 Jan 25;260(2):1311–1325. [PubMed] [Google Scholar]
- JOHNSON A. B., STRECKER H. J. The interconversion of glutamic acid and proline. IV. The oxidation of proline by rat liver mitochondria. J Biol Chem. 1962 Jun;237:1876–1882. [PubMed] [Google Scholar]
- Kosugi K., Harano Y., Nakano T., Suzuki M., Kashiwagi A., Shigeta Y. Mechanism of adrenergic stimulation of hepatic ketogenesis. Metabolism. 1983 Nov;32(11):1081–1087. doi: 10.1016/0026-0495(83)90081-1. [DOI] [PubMed] [Google Scholar]
- Latipä P. M., Kärki T. T., Hiltunen J. K., Hassinen I. E. Regulation of palmitoylcarnitine oxidation in isolated rat liver mitochondria. Role of the redox state of NAD(H). Biochim Biophys Acta. 1986 Feb 12;875(2):293–300. doi: 10.1016/0005-2760(86)90179-7. [DOI] [PubMed] [Google Scholar]
- Ly S., Kim K. H. Inactivation of hepatic acetyl-CoA carboxylase by catecholamine and its agonists through the alpha-adrenergic receptors. J Biol Chem. 1981 Nov 25;256(22):11585–11590. [PubMed] [Google Scholar]
- McCormack J. G. Characterization of the effects of Ca2+ on the intramitochondrial Ca2+-sensitive enzymes from rat liver and within intact rat liver mitochondria. Biochem J. 1985 Nov 1;231(3):581–595. doi: 10.1042/bj2310581. [DOI] [PMC free article] [PubMed] [Google Scholar]
- McCormack J. G. Evidence that adrenaline activates key oxidative enzymes in rat liver by increasing intramitochondrial [Ca2+]. FEBS Lett. 1985 Jan 28;180(2):259–264. doi: 10.1016/0014-5793(85)81082-6. [DOI] [PubMed] [Google Scholar]
- Osmundsen H. Spectrophotometric procedure for measuring mitochondrial beta-oxidation. Methods Enzymol. 1981;72:306–314. doi: 10.1016/s0076-6879(81)72020-2. [DOI] [PubMed] [Google Scholar]
- Otto D. A., Ontko J. A. Structure-function relations between fatty acid oxidation and the mitochondrial inner-membrane--matrix region. Eur J Biochem. 1982 Dec 15;129(2):479–485. doi: 10.1111/j.1432-1033.1982.tb07074.x. [DOI] [PubMed] [Google Scholar]
- Quinlan P. T., Halestrap A. P. The mechanism of the hormonal activation of respiration in isolated hepatocytes and its importance in the regulation of gluconeogenesis. Biochem J. 1986 Jun 15;236(3):789–800. doi: 10.1042/bj2360789. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Quinlan P. T., Thomas A. P., Armston A. E., Halestrap A. P. Measurement of the intramitochondrial volume in hepatocytes without cell disruption and its elevation by hormones and valinomycin. Biochem J. 1983 Aug 15;214(2):395–404. doi: 10.1042/bj2140395. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ruzicka F. J., Beinert H. A new iron-sulfur flavoprotein of the respiratory chain. A component of the fatty acid beta oxidation pathway. J Biol Chem. 1977 Dec 10;252(23):8440–8445. [PubMed] [Google Scholar]
- Saggerson E. D. Carnitine acyltransferase activities in rat liver and heart measured with palmitoyl-CoA and octanoyl-CoA. Latency, effects of K+, bivalent metal ions and malonyl-CoA. Biochem J. 1982 Feb 15;202(2):397–405. doi: 10.1042/bj2020397. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Saggerson E. D. Does fasting decrease the inhibitory effect of malonyl-CoA on hepatic beta-oxidation? Biochem J. 1982 Nov 15;208(2):525–528. doi: 10.1042/bj2080525. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Siess E. A., Brocks D. G., Lattke H. K., Wieland O. H. Effect of glucagon on metabolite compartmentation in isolated rat liver cells during gluconeogenesis from lactate. Biochem J. 1977 Aug 15;166(2):225–235. doi: 10.1042/bj1660225. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Siess E. A., Brocks D. G., Wieland O. H. Comparative studies on the influence of hormones on metabolite compartmentation in isolated liver cells during gluconeogenesis from lactate. Biochem Soc Trans. 1978;6(6):1139–1144. doi: 10.1042/bst0061139. [DOI] [PubMed] [Google Scholar]
- Siess E. A., Brocks D. G., Wieland O. H. Distinctive effects of glucagon on gluconeogenesis and ketogenesis in hepatocytes isolated from normal and biotin-deficient rats. Biochem J. 1978 Jun 15;172(3):517–521. doi: 10.1042/bj1720517. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Staddon J. M., McGivan J. D. Distinct effects of glucagon and vasopressin on proline metabolism in isolated hepatocytes. The role of oxoglutarate dehydrogenase. Biochem J. 1984 Jan 15;217(2):477–483. doi: 10.1042/bj2170477. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Stanley K. K., Tubbs P. K. The role of intermediates in mitochondrial fatty acid oxidation. Biochem J. 1975 Jul;150(1):77–88. doi: 10.1042/bj1500077. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Stoner C. D. Steady-state kinetics of the overall oxidative phosphorylation reaction in heart mitochondria. Evidence for linkage of the energy-yielding and energy-consuming steps by freely diffusible intermediates and for an allosteric mechanism of respiratory control at coupling site 2. J Bioenerg Biomembr. 1985 Apr;17(2):85–108. doi: 10.1007/BF00744200. [DOI] [PubMed] [Google Scholar]
- Strzelecki T., Thomas J. A., Koch C. D., LaNoue K. F. The effect of hormones on proton compartmentation in hepatocytes. J Biol Chem. 1984 Apr 10;259(7):4122–4129. [PubMed] [Google Scholar]
- Sugden M. C., Ball A. J., Ilic V., Williamson D. H. Stimulation of [1-14C]oleate oxidation to 14CO2 in isolated rat hepatocytes by vasopressin: effects of Ca2+. FEBS Lett. 1980 Jul 11;116(1):37–40. doi: 10.1016/0014-5793(80)80523-0. [DOI] [PubMed] [Google Scholar]
- Sugden M. C., Watts D. I. Stimulation of [1-14C]oleate oxidation to 14CO2 in isolated rat hepatocytes by the catecholamines, vasopressin and angiotensin. A possible mechanism of action. Biochem J. 1983 Apr 15;212(1):85–91. doi: 10.1042/bj2120085. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Taylor W. M., Reinhart P. H., Bygrave F. L. Stimulation by alpha-adrenergic agonists of Ca2+ fluxes, mitochondrial oxidation and gluconeogenesis in perfused rat liver. Biochem J. 1983 Jun 15;212(3):555–565. doi: 10.1042/bj2120555. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Taylor W. M., van de Pol E., Bygrave F. L. The stimulation of tricarboxylic acid-cycle flux by alpha-adrenergic agonists in perfused rat liver. Biochem J. 1986 Jan 15;233(2):321–324. doi: 10.1042/bj2330321. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Whipps D. E., Halestrap A. P. Rat liver mitochondria prepared in mannitol media demonstrate increased mitochondrial volumes compared with mitochondria prepared in sucrose media. Relationship to the effect of glucagon on mitochondrial function. Biochem J. 1984 Jul 1;221(1):147–152. doi: 10.1042/bj2210147. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Williamson J. R., Browning E. T., Thurman R. G., Scholz R. Inhibition of glucagon effects in perfused rat liver by (+)decanoylcarnitine. J Biol Chem. 1969 Sep 25;244(18):5055–5064. [PubMed] [Google Scholar]
