title: Bafilomycin A1 is a potassium ionophore that impairs mitochondrial functions.
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.
authors.affiliation: Department of Applied Chemistry and Microbiology, University of Helsinki, Viikki Biocenter 1, POB 56, Helsinki 00014, Finland.
authors.forename: Vera V
authors.initials: VV
authors.lastname: Teplova
authors.forename: Anton A
authors.initials: AA
authors.lastname: Tonshin
authors.forename: Pavel A
authors.initials: PA
authors.lastname: Grigoriev
authors.forename: Nils-Erik L
authors.initials: NE
authors.lastname: Saris
authors.forename: Mirja S
authors.initials: MS
authors.lastname: Salkinoja-Salonen
mesh_terms: D000818:Animals; D004791:Enzyme Inhibitors / Q000494:pharmacology; D066298:In Vitro Techniques; D017136:Ion Transport / Q000187:drug effects; D007476:Ionophores / Q000494:pharmacology*; D018942:Macrolides / Q000494:pharmacology*; D008297:Male; D008930:Mitochondria, Liver / Q000187:drug effects* / Q000378:metabolism*; D011188:Potassium / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D025262:Vacuolar Proton-Translocating ATPases / Q000037:antagonists & inhibitors
chemical_list: D004791:Enzyme Inhibitors; D007476:Ionophores; D018942:Macrolides; C040929:bafilomycin A1; D025262:Vacuolar Proton-Translocating ATPases; D011188:Potassium