Skip to main content
Log in

Swelling of normal, preneoplastic and neoplastic liver mitochondria

I. Spontaneous and thyroxine-induced swelling of normal liver mitochondria as affected by succinate and adenine nucleotides

  • Published:
Zeitschrift für Krebsforschung Aims and scope Submit manuscript

Summary

The swelling of rat and mouse liver mitochondria, isolated in 0.30 M sucrose and incubated in sucrose-Tris of pH 7.4 at 22±1°C, in response to succinate, adenine nucleotides (10−5 M), malonate, thyroxine, and DNP, separately or in various combinations, was measured.

It was found that both the spontaneous and thyroxine-induced swelling of fresh mitochondria were counteracted by succinate and, to a still greater extent, by succinate plus adenine nucleotide (ADP≥ATP≫ or > AMP). The protection was abolished by malonate or DNP. The protection against swelling afforded by succinate to fresh mitochondria was followed by a phase of rapid swelling. Progressive ageing or frequent washing of the particles, prior to their incubation, led to a reduction or abolition of the protective effect. It was concluded that mitochondrial swelling was governed by the degree of intrinsic stability of the isolated particles.

Zusammenfassung

Die Schwellung von in 0,30 M Saccharose isolierten und in Saccharose-Tris von pH 7,4 bei 22±1°C inkubierten Mitochondrien aus Mäuse- und Rattenlebern wurde gemessen nach Zusatz von Succinat, Adeninnucleotiden (10−5 M), Malonat, Thyroxin und DNP, allein und in verschiedenen Kombinationen. Sowohl die spontane wie die thyroxininduzierte Schwellung frischer Mitochondrien wird durch Succinat und noch mehr durch Succinat und Adeninnucleotide (ADP≥ATP≫ oder > AMP) gehemmt. Die Hemmung wird aufgehoben durch Malonat oder DPN. Auf die Hemmung der Schwellung von frischen Mitochondrien durch Succinat folgt eine Phase schneller Schwellung. Allmähliche Alterung oder wiederholte Waschungen von den Mitochondrien vor der Inkubation führen zu einer Verringerung oder Aufhebung des hemmenden Effektes des Succinats.

Daraus wird gefolgert, daß die mitochondriale Schwellung von dem Grade der Eigenstabilität der isolierten Partikel abhängig ist.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

Abbreviations

O.D.520 :

optical density at 520 mμ

EDTA:

ethylenediamine tetra-acetate

AMP, ADP and ATP:

adenosine mono-,-di- and-triphosphates

Tris:

2-amino-2-hydroxymethylpropane-1:3-diolchloride

DPN:

diphosphopyridine nucleotide

DNP:

2:4-dinitrophenol

References

  • Baltscheffsky, H.: Mitochondrial oxidative phosphorylation in a magnesium-free medium. Biochim. Biophys. Acta, 20, 434 (1956).

    Google Scholar 

  • Baltscheffsky, H.: Mitochondrial respiratory control and phosphorylative activities in a magnesium-free medium. Biochim. biophys. Acta 25, 382 (1957).

    Google Scholar 

  • Beyer, R. E., L. Ernster, H. Löw and T. Beyer: Correlation of optical density and oxidative phosphorylation in reconstructed mitochondrial systems. Exp. Cell Res. 8, 586 (1955).

    Google Scholar 

  • Brenner-Holzach, O., and J. Raaflaub: Die Korrelation zwischen der Schwellung isolierter Mitochondrien und dem Abbau der intramitochondrialen Adenosinnucleotide. Helv. physiol. pharmacol. Acta 12, 242 (1954).

    Google Scholar 

  • Chappell, J. B., and G. D. Greville: Dependence of mitochondrial swelling on oxidizable substrates. Nature (Lond.) 182, 813 (1958).

    Google Scholar 

  • Chappell, J. B., and G. D. Greville: Inhibition of electron transport and the swelling of isolated mitochondria. Nature (Lond.) 183, 1525 (1959).

    Google Scholar 

  • Chappell, J. B., and G. D. Greville: Effects of 2:4-dinitrophenol and other agents on the swelling of isolated mitochondria. Nature (Lond.) 183, 1737 (1959).

    Google Scholar 

  • Chappell, J. B., and G. D. Greville: Mitochondrial swelling and electron transport. Biochim. biophys. Acta 38, 483 (1960).

    Google Scholar 

  • Cooper, C., and D. F. Tapley: Swelling of mitochondria isolated from different tissues. Biochim. biophys. Acta 25, 426 (1957).

    Google Scholar 

  • Corwin, L. M., and M. N. Lipsett: Relation of the electron transport system to swelling. J. biol. Chem. 234, 2453 (1959).

    Google Scholar 

  • DiSabato, G., and A. Fonnesu: Metabolic mechanisms involved in the swelling of isolated mitochondria and its prevention. Biochim. biophys. Acta 35, 358 (1959).

    Google Scholar 

  • Emmelot, P., and C. J. Bos: Thyroxine-mediated release of diphosphopyridine nucleotide from mitochondrial dehydrogenases. Exp. Cell Res. 14, 132 (1958).

    Google Scholar 

  • Emmelot, P., and C. J. Bos: The metabolism of neoplastic tissues: The effect of 2:4-dinitrophenol on the respiration of ascites tumor cells. Brit. J. Cancer 13, 520 (1959).

    Google Scholar 

  • Emmelot, P., C. J. Bos, P. J. Brombacher and J. F. Hampe: Studies on isolated tumor mitochondria: Biochemical properties of mitochondria from hepatomas with special reference to a transplanted rat hepatoma of the solid type. Brit. J. Cancer 13, 348 (1959).

    Google Scholar 

  • Emmelot, P., C. J. Bos, P. J. Brombacher and I. H. M. Reyers: Swelling of fresh and aged mitochondria as affected by succinate, adenine nucleotides and thyroxine. Nature (Lond.) 186, 556 (1960).

    Google Scholar 

  • Emmelot, P., C. J. Bos and I. H. M. Reyers: Z. Krebsforsch. 64, 52 (1960).

    Google Scholar 

  • Emmelot, P., and I. H. M. Reyers: Z. Krebsforsch. 64, 35 (1960).

    Google Scholar 

  • Ernster, L.: Distribution and interaction of enzymes within animal cells. Biochem. Soc. Symp. 16, 54 (1959).

    Google Scholar 

  • Ernster, L., and H. Low: Reconstruction of oxidative phosphorylation in aged mitochondrial systems. Exp. Cell Res., Suppl. 3, 133 (1955).

    Google Scholar 

  • Fawcett, D. W.: Observations on the cytology and electron microscopy of hepatic cells. J. Nat. Cancer Inst. 15 (Suppl.), 1475 (1955).

    Google Scholar 

  • Fonnesu, A., and R. E. Davies: The prevention of swelling of liver mitochondria in vitro. Biochem. J. 64, 769 (1956).

    Google Scholar 

  • Gansler, H., and Ch. Rouiller: Modifications physiologiques et pathologiques du chondriome. Schweiz. Z. Path. 19, 217 (1956).

    Google Scholar 

  • Greengard, P., K. Minnaert, E. C. Slater and I. Betel: Yield of oxidative phosphorylation associated with the oxidation of succinate to fumarate. Biochem. J. 73, 637 (1959).

    Google Scholar 

  • Harman, J. W., and M. Feigelson: Studies on mitochondria: V. The relationship of structure and oxidative phosphorylation in mitochondria of heart muscle. Exp. Cell Res. 3, 509 (1952).

    Google Scholar 

  • Hoch, F. L., and F. Lipmann: The uncoupling of respiration and phosphorylation by thyroid hormones. Proc. nat. Acad. Sci. (Wash.) 40, 909 (1954).

    Google Scholar 

  • Hunter jr., F. E., J. Davis and L. Carlat: The stability of oxidative and phosphorylative systems in mitochondria under anaerobic conditions. Biochim. biophys. Acta 20, 237 (1956).

    Google Scholar 

  • Hunter jr., F. E., and L. Ford: Inactivation of oxidative and phosphorylative systems in mitochondria by preincubation with phosphate and other ions. J. biol. Chem. 216, 357 (1955).

    Google Scholar 

  • Hunter jr., F. E., J. F. Levy, J. Fink, B. Schultz, F. Guerra and A. Hurwitz: Studies on the mechanism by which anaerobiosis prevents swelling of mitochondria in vitro: Effect of electron transport chain inhibitors. J. biol. Chem. 234, 2176 (1959).

    Google Scholar 

  • Kaufman, B. T., and N. O. Kaplan: Effects of substrates on the swelling and loss of pyridine nucleotides from rat liver mitochondria. Biochim. biophys. Acta 32, 576 (1959); 39, 332 (1960).

    Google Scholar 

  • Laudahn, G.: Die oxydative Phosphorylierung isolierter Mitochondrien und ihre Abhängigkeit von strukturgebundenen Faktoren. Experientia (Basel) 15, 71 (1959).

    Google Scholar 

  • Laudahn, G., and E. Rasch: Die Korrelation zwischen Atmungsketten-Phosphorylierung und Konzentration intramitochondrialer Adenosinnucleotide bei isolierten Leberzell-Mitochondrien. Biochem. Z. 330, 509 (1958).

    Google Scholar 

  • Lehninger, A. L.: In: Enzymes: Units of biological structure and function (O. H. Gaebler, ed.), p. 217. New York: Academic Press, Inc. 1956.

    Google Scholar 

  • Lehninger, A. L.: Reversal of thyroxine-induced swelling of rat liver mitochondria by ATP. J. biol. Chem. 234, 2187 (1959).

    Google Scholar 

  • Lehninger, A. L.: Reversal of various types of mitochondrial swelling by ATP. J. biol. Chem. 234, 2465 (1959).

    Google Scholar 

  • Lehninger, A. L., B. L. Ray and M. Schneider: The swelling of rat liver mitochondria by thyroxine and its reversal. J. biophys. biochem. Cytol. 5, 97 (1959).

    Google Scholar 

  • Lipsett, M. W., and L. M. Corwin: Studies on stability of rat liver mitochondria. I. Role of oxidative phosphorylation in swelling. J. biol. Chem. 234, 2448 (1959).

    Google Scholar 

  • Park, J. H., B. P. Meriwether, C. R. Park, S. H. Mudd and F. Lipmann: Glutathione and ethylenediaminetetraacetate antagonism of uncoupling of oxidative phosphorylation. Biochim. biophys. Acta 22, 403 (1956).

    Google Scholar 

  • Raaflaub, J.: Die Schwellung isolierter Leberzellmitochondrien und ihre physikalisch-chemische Beeinflußbarkeit. Helv. physiol. pharmacol. Acta 11, 142 (1953).

    Google Scholar 

  • Tapley, D. F.: The effect of thyroxine and other substances on the swelling of isolated rat liver mitochondria. J. biol. Chem. 222, 325 (1956).

    Google Scholar 

  • Tujimara, H.: Electron microscopie studies on the DAB-induced hepatoma. Med. J. Osaka Univ. 9, 115 (1958). Excerpta med. (Amst.), Sect. XVI, 8, 395 (1960).

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Emmelot, P., Bos, C.J. & Reyers, I.H.M. Swelling of normal, preneoplastic and neoplastic liver mitochondria. Z Krebs-forsch 64, 22–34 (1960). https://doi.org/10.1007/BF00524274

Download citation

  • Received:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00524274

Keywords

Navigation