• We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
Logo of aacPermissionsJournals.ASM.orgJournalAAC ArticleJournal InfoAuthorsReviewers
Antimicrob Agents Chemother. Apr 1976; 9(4): 655–660.
PMCID: PMC429593

Salinomycin Effects on Mitochondrial Ion Translocation and Respiration

Abstract

The effects of salinomycin on alkali cation transport and membrane functions in rat liver mitochondria have been investigated. After potassium uptake, stimulated by valinomycin or monazomycin in the presence of adenosine 5′-triphosphate, salinomycin caused rapid release of K+ from mitochondria. Salinomycin reversed valinomycin- or monazomycin-induced oscillatory swelling of mitochondria preloaded with K+, Rb+, and Na+ but was without effect on Li+ or Cs+ preloaded mitochondria. Salinomycin blocked the retention of K+ more effectively than the retention of Rb+ or Na+. Salinomycin inhibited both coupled and uncoupled respiration with strict substrate specificity in medium of low but not in high K+ concentration. The oxidation of glutamate, α-ketoglutarate, and malate plus pyruvate was inhibited by salinomycin, but that of β-hydroxybutyrate or succinate was not significantly affected. Salinomycin inhibited adenosine triphosphatase activity of mitochondria induced by valinomycin or monazomycin in K+ and Rb+ medium without significantly affecting adenosine triphosphatase activity in Li+, Na+, or Cs+ medium. Oxidative phosphorylation in mitochondria was inhibited by salinomycin but the inhibitory effect of salinomycin lacked the substrate specificity observed for respiration. It is proposed that salinomycin perturbs mitochondrial functions by acting as a mobile carrier for alkali cations through membranes.

Full text

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (835K), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Ashton R, Steinrauf LK. Thermodynamic consideration of the ion transporting antibiotics. J Mol Biol. 1970 May 14;49(3):547–556. [PubMed]
  • Caswell AH, Pressman BC. Kinetics of transport of divalent cations across sarcoplasmic reticulum vesicles induced by ionophores. Biochem Biophys Res Commun. 1972 Oct 6;49(1):292–298. [PubMed]
  • Duffus JH, Patterson LJ. Control of cell division in yeast using the ionophore, A23187 with calcium and magnesium. Nature. 1974 Oct 18;251(5476):626–627. [PubMed]
  • Estrada-O S, Calderón E. Potassium and proton movements in relation to the energy-linked transport of phosphate in liver mitochondria. Biochemistry. 1970 May 12;9(10):2092–2099. [PubMed]
  • Feinman RD, Detwiler TC. Platelet secretion induced by divalent cation ionophores. Nature. 1974 May 10;249(453):172–173. [PubMed]
  • Gómez-Puyou A, Sandoval F, Chávez E, Tuena M. On the role of K+ on oxidative phosphorylation. J Biol Chem. 1970 Oct 25;245(20):5239–5247. [PubMed]
  • Gómez-Puyou A, Sandoval F, De Gómez-Puyou MT, Peña A, Chávez E. Coupling of oxidative phosphorylation by monovalent cations. Biochemistry. 1972 Jan 4;11(1):97–102. [PubMed]
  • Graven SN, Estrada-O S, Lardy HA. Alkali metal cation release and respiratory inhibition induced by nigericin in rat liver mitochondria. Proc Natl Acad Sci U S A. 1966 Aug;56(2):654–658. [PMC free article] [PubMed]
  • Harold FM, Altendorf KH, Hirata H. Probing membrane transport mechanisms with inophores. Ann N Y Acad Sci. 1974 May 10;235(0):149–160. [PubMed]
  • Lardy H. Influence of antibiotics and cyclic polyethers on ion transport in mitochondria. Fed Proc. 1968 Nov-Dec;27(6):1278–1282. [PubMed]
  • Lardy HA, Graven SN, Estrada S. Specific induction and inhibition of cation and anion transport in mitochondria. Fed Proc. 1967 Sep;26(5):1355–1360. [PubMed]
  • Levy JV, Cohen JA, Inesi G. Contractile effects of a calcium ionophore. Nature. 1973 Apr 13;242(5398):461–463. [PubMed]
  • LOWRY OH, ROSEBROUGH NJ, FARR AL, RANDALL RJ. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed]
  • Luckasen JR, White JG, Kersey JH. Mitogenic properties of a calcium ionophore, A23187. Proc Natl Acad Sci U S A. 1974 Dec;71(12):5088–5090. [PMC free article] [PubMed]
  • Maino VC, Green NM, Crumpton MJ. The role of calcium ions in initiating transformation of lymphocytes. Nature. 1974 Sep 27;251(5473):324–327. [PubMed]
  • Massini P, Lüscher EF. Some effects of ionophores for divalent cations on blood platelets. Comparison with the effects of thrombin. Biochim Biophys Acta. 1974 Nov 4;372(1):109–121. [PubMed]
  • Miyazaki Y, Shibuya M, Sugawara H, Kawaguchi O, Hirsoe C. Salinomycin, a new polyether antibiotic. J Antibiot (Tokyo) 1974 Nov;27(11):814–821. [PubMed]
  • Mitani M, Yamanishi T, Miyazaki Y. Salinomycin: a new monovalent cation ionophore. Biochem Biophys Res Commun. 1975 Oct 27;66(4):1231–1236. [PubMed]
  • NIELSEN SO, LEHNINGER AL. Phosphorylation coupled to the oxidation of ferrocytochrome c. J Biol Chem. 1955 Aug;215(2):555–570. [PubMed]
  • Pressman BC. Ionophorous antibiotics as models for biological transport. Fed Proc. 1968 Nov-Dec;27(6):1283–1288. [PubMed]
  • Pressman BC. Properties of ionophores with broad range cation selectivity. Fed Proc. 1973 Jun;32(6):1698–1703. [PubMed]
  • Pressman BC, Harris EJ, Jagger WS, Johnson JH. Antibiotic-mediated transport of alkali ions across lipid barriers. Proc Natl Acad Sci U S A. 1967 Nov;58(5):1949–1956. [PMC free article] [PubMed]
  • PRESSMAN BC, LARDY HA. Influence of potassium and other alkali cations on respiration of mitochondria. J Biol Chem. 1952 May;197(2):547–556. [PubMed]
  • Reed PW, Lardy HA. A23187: a divalent cation ionophore. J Biol Chem. 1972 Nov 10;247(21):6970–6977. [PubMed]
  • Rottenberg H, Scarpa A. Calcium uptake and membrane potential in mitochondria. Biochemistry. 1974 Nov 5;13(23):4811–4817. [PubMed]
  • Shavit N, San Pietro A. K+ -dependent uncoupling of photophosphorylation by nigericin. Biochem Biophys Res Commun. 1967 Jul 21;28(2):277–283. [PubMed]
  • Ueda I, Wada T. Determination of inorganic phosphate by the molybdovanadate method in the presence of ATP and some interfering organic bases. Anal Biochem. 1970 Sep;37(1):169–174. [PubMed]

Articles from Antimicrobial Agents and Chemotherapy are provided here courtesy of American Society for Microbiology (ASM)

Formats:

Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...

Links

  • Compound
    Compound
    PubChem Compound links
  • MedGen
    MedGen
    Related information in MedGen
  • PubMed
    PubMed
    PubMed citations for these articles
  • Substance
    Substance
    PubChem Substance links

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...