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Bafilomycin A1 is a potassium ionophore that impairs mitochondrial functions

Journal of Bioenergetics and Biomembranes volume 39, Article number: 321 (2007) Cite this article

Abstract

Novel activities of bafilomycin A1, a macrolide antibiotic known as an inhibitor of V-ATPases, were discovered. Bafilomycin A1 induced uptake of potassium ions by energized mitochondria and caused mitochondrial swelling, loss of membrane potential, uncoupling of oxidative phosphorylation, inhibition of the maximal respiration rates, and induced pyridine nucleotide oxidation. The mitochondrial effects provoked by nanomolar concentrations of bafilomycin A1 were connected to its activity as a potent, K+-specific ionophore. The K+ ionophoric activity of bafilomycin A1 was observed also in black lipid membranes, indicating that it was an inherent property of the bafilomycin A1 molecule. It was found that bafilomycin A1 is a K+ carrier but not a channel former. Bafilomycin A1 is the first and currently unique macrolide antibiotic with K+ ionophoric properties. The novel properties of bafilomycin A1 may explain some of the biological effects of this plecomacrolide antibiotic, independent of V-ATPase inhibition.

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Affiliations

  1. Department of Applied Chemistry and Microbiology, University of Helsinki, Viikki Biocenter 1, POB 56, Helsinki, 00014, Finland

    Vera V. Teplova, Anton A. Tonshin, Pavel A. Grigoriev, Nils-Erik L. Saris & Mirja S. Salkinoja-Salonen

  2. Institute of Theoretical and Experimental Biophysics, Russian Academy of Sciences, 142290, Pushchino, Moscow Region, Russia

    Vera V. Teplova

  3. Institute of Cell Biophysics, Russian Academy of Sciences, 142290, Pushchino, Moscow Region, Russia

    Pavel A. Grigoriev

  4. A. N. Belozersky Institute of Physico-Chemical Biology, Moscow State University, 119899, Moscow, Russia

    Anton A. Tonshin

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  1. Vera V. Teplova
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  2. Anton A. Tonshin
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  3. Pavel A. Grigoriev
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  4. Nils-Erik L. Saris
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  5. Mirja S. Salkinoja-Salonen
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Correspondence to Mirja S. Salkinoja-Salonen.

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Teplova, V.V., Tonshin, A.A., Grigoriev, P.A. et al. Bafilomycin A1 is a potassium ionophore that impairs mitochondrial functions. J Bioenerg Biomembr 39, 321 (2007). https://doi.org/10.1007/s10863-007-9095-9

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  • DOI: https://doi.org/10.1007/s10863-007-9095-9

Keywords

  • Macrolide antibiotics
  • V-ATPase inhibitor
  • Mitochondriotoxic
  • K+ influx
  • Mitochondrial swelling
  • ΔΨm drop
  • Uncoupling, black lipid membrane
  • Ionophore, potassium carrier