title: Development of a yeast bio-assay to screen anti-mitochondrial drugs.
abstract: Previous studies show that acetylsalicylic acid (aspirin) at low concentrations affects yeast sexual structure development in a similar fashion than oxygen depletion. This is ascribed to its anti-mitochondrial action. In this study, we report the same for other anti-inflammatory (i.e. ibuprofen, indomethacin, salicylic acid, benzoic acid) as well as anticancer (Lonidamine) drugs, also known for inhibiting mitochondrial activity in mammalian cells. This is shown by a unique yeast bio-assay, with the mitochondrion-dependent sexual structure, riboflavin production, and hyphal morphology of the yeast Eremothecium ashbyi serving as indicators. These drugs affect this yeast in a similar way as found under oxygen limitation conditions by inhibiting sexual structure development (most sensitive), riboflavin production, and yielding characteristically wrinkled and granular hyphae, presenting a unique "anoxic" morphological pattern for this yeast. Only drugs associated with anti-mitochondrial activity presented such a pattern. This bio-assay may find application in the screening for novel drugs from various sources with anti-mitochondrial actions.
authors.affiliation: Department of Microbial, Biochemical and Food Biotechnology, University of The Free State, P.O. Box 339, Bloemfontein, 9301, South Africa. Kockjl.sci@ufs.ac.za
authors.forename: Johan L F
authors.initials: JL
authors.lastname: Kock
authors.forename: Chantel W
authors.initials: CW
authors.lastname: Swart
authors.forename: Desmond M
authors.initials: DM
authors.lastname: Ncango
authors.forename: Johan L F
authors.initials: JL
authors.lastname: Kock
authors.forename: Ingrid A
authors.initials: IA
authors.lastname: Munnik
authors.forename: Marleen M J
authors.initials: MM
authors.lastname: Maartens
authors.forename: Carolina H
authors.initials: CH
authors.lastname: Pohl
authors.forename: Pieter W J
authors.initials: PW
authors.lastname: van Wyk
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D000935:Antifungal Agents / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology; D001681:Biological Assay / Q000379:methods*; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D055169:Eremothecium / Q000166:cytology / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D007191:Indazoles / Q000494:pharmacology*; D008928:Mitochondria / Q000187:drug effects*; D010100:Oxygen / Q000378:metabolism; D054883:Oxylipins / Q000378:metabolism
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000935:Antifungal Agents; D000970:Antineoplastic Agents; D007191:Indazoles; D054883:Oxylipins; D010100:Oxygen; C016371:lonidamine