title: Electrogenic and nonelectrogenic ion fluxes across lipid and mitochondrial membranes mediated by monensin and monensin ethyl ester.
abstract: Monensin is a carrier of cations through lipid membranes capable of exchanging sodium (potassium) cations for protons by an electroneutral mechanism, whereas its ethyl ester derivative ethyl-monensin is supposed to transport sodium (potassium) cations in an electrogenic manner. To elucidate mechanistic details of the ionophoric activity, ion fluxes mediated by monensin and ethyl-monensin were measured on planar bilayer lipid membranes, liposomes, and mitochondria. In particular, generation of membrane potential on liposomes was studied via the measurements of rhodamine 6G uptake by fluorescence correlation spectroscopy. In mitochondria, swelling experiments were expounded by the additional measurements of respiration, membrane potential, and matrix pH. It can be concluded that both monensin and ethyl-monensin can perform nonelectrogenic exchange of potassium (sodium) ions for protons and serve as electrogenic potassium ion carriers similar to valinomycin. The results obtained are in line with the predictions based on the crystal structures of the monensin complexes with sodium ions and protons (Huczyński et al., Biochim. Biophys. Acta, 1818 (2012) pp. 2108-2119). The functional activity observed for artificial membranes and mitochondria can be applied to explain the activity of ionophores in living systems. It can also be important for studying the antitumor activity of monensin.
authors.affiliation: A.N. Belozersky Institute of Physico-Chemical Biology, M.V. Lomonosov Moscow State University, Leninskie Gory 1, Moscow 119991, Russia. Electronic address: antonen@genebee.msu.ru.
authors.forename: Yuri N
authors.initials: YN
authors.lastname: Antonenko
authors.affiliation: A.N. Belozersky Institute of Physico-Chemical Biology, M.V. Lomonosov Moscow State University, Leninskie Gory 1, Moscow 119991, Russia.
authors.forename: Tatyana I
authors.initials: TI
authors.lastname: Rokitskaya
authors.affiliation: Department of Bioorganic Chemistry, Faculty of Chemistry, A. Mickiewicz University, Umultowska 89b, 61-614 Poznan, Poland.
authors.forename: Adam
authors.initials: A
authors.lastname: Huczyński
mesh_terms: D000818:Animals; D001692:Biological Transport / Q000187:drug effects*; D019069:Cell Respiration / Q000187:drug effects; D006863:Hydrogen-Ion Concentration; D007474:Ion Exchange; D007476:Ionophores / Q000494:pharmacology; D007700:Kinetics; D008051:Lipid Bilayers / Q000378:metabolism; D008081:Liposomes; D008563:Membrane Lipids / Q000737:chemistry / Q000378:metabolism; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008567:Membranes, Artificial; D008930:Mitochondria, Liver / Q000187:drug effects / Q000378:metabolism*; D051336:Mitochondrial Membranes / Q000378:metabolism; D008933:Mitochondrial Swelling / Q000187:drug effects; D008985:Monensin / Q000737:chemistry* / Q000494:pharmacology*; D009550:Nigericin / Q000494:pharmacology; D010743:Phospholipids / Q000737:chemistry / Q000378:metabolism; D011188:Potassium / Q000378:metabolism; D061209:Proton Ionophores / Q000737:chemistry / Q000494:pharmacology; D011522:Protons; D051381:Rats; D012964:Sodium / Q000378:metabolism; D014634:Valinomycin / Q000494:pharmacology
chemical_list: D007476:Ionophores; D008051:Lipid Bilayers; D008081:Liposomes; D008563:Membrane Lipids; D008567:Membranes, Artificial; D010743:Phospholipids; D061209:Proton Ionophores; D011522:Protons; D014634:Valinomycin; D008985:Monensin; D012964:Sodium; D009550:Nigericin; D011188:Potassium
keywords: Cation transport; Ionophore; Membrane potential; Mitochondria respiration