title: The Fusarium mycotoxins enniatins and beauvericin cause mitochondrial dysfunction by affecting the mitochondrial volume regulation, oxidative phosphorylation and ion homeostasis.
abstract: The mechanisms of cell toxicity of mycotoxins of the enniatin family produced by Fusarium sp. enniatin B, a mixture of enniatin homologues (3% A, 20% A(1), 19% B, 54% B1) and beauvericin, were investigated. In isolated rat liver mitochondria, exposure to submicromolar concentrations of the enniatin mycotoxins depleted the mitochondrial transmembrane potential, uncoupled oxidative phosphorylation, induced mitochondrial swelling and decreased calcium retention capacity of the mitochondria. The mitochondrial effects were strongly connected with the potassium (K(+)) ionophoric activity of the enniatins. The observed enniatins induced K(+) uptake by mitochondria. This shows that the enniatins acted as ionophores highly selective for potassium ions. The effects were observed in potassium containing media whereas less or no effect remained to be observed when K(+) was partially or totally replaced by isomolar concentrations of Na(+). The rank order of enniatin induced mitochondrial impairment was beauvericin>enniatin mixture>enniatin B. Exposure to the enniatins depleted the mitochondrial membrane potential also in intact human neural (Paju), murine insulinoma (Min-6) cells as well as boar spermatozoa. Exposure to enniatin B in media with physiological (4mM) or low (<1mM) but not in high (60mM) external concentration of K(+) induced hyperpolarization of the spermatozoal plasma membrane indicating enniatin that catalysed efflux of the cytosolic K(+) ions. These results indicate that the cellular toxicity targets of the enniatin mycotoxins are the mitochondrion and the homeostasis of potassium ions.
authors.affiliation: Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow RU-119899, Russia.
authors.forename: Anton A
authors.initials: AA
authors.lastname: Tonshin
authors.forename: Vera V
authors.initials: VV
authors.lastname: Teplova
authors.forename: Maria A
authors.initials: MA
authors.lastname: Andersson
authors.forename: Mirja S
authors.initials: MS
authors.lastname: Salkinoja-Salonen
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D002415:Cats; D002478:Cells, Cultured; D047630:Depsipeptides / Q000302:isolation & purification / Q000633:toxicity*; D005670:Fusarium / Q000737:chemistry*; D006706:Homeostasis / Q000187:drug effects; D006801:Humans; D007340:Insulinoma / Q000378:metabolism; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D051379:Mice; D008930:Mitochondria, Liver / Q000187:drug effects* / Q000378:metabolism; D009183:Mycotoxins / Q000302:isolation & purification / Q000633:toxicity*; D009474:Neurons / Q000378:metabolism; D010085:Oxidative Phosphorylation / Q000187:drug effects; D011188:Potassium / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013094:Spermatozoa / Q000187:drug effects / Q000378:metabolism; D013552:Swine
chemical_list: D047630:Depsipeptides; D009183:Mycotoxins; C100264:enniatins; C004456:beauvericin; D011188:Potassium; D002118:Calcium