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Development of a yeast bio-assay to screen anti-mitochondrial drugs
Johan L F Kock1, Chantel W Swart, Desmond M Ncango
1Department of Microbial, Biochemical and Food Biotechnology, University of The Free State, P.O. Box 339, Bloemfontein, 9301, South Africa. Kockjl.sci@ufs.ac.za
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.
Insights
Several drugs inhibit yeast sexual development, mimicking oxygen depletion. This unique yeast bio-assay identifies compounds with anti-mitochondrial activity, useful for drug screening.
Area of Science:
- Microbiology
- Biochemistry
- Pharmacology
Background:
- Acetylsalicylic acid (aspirin) at low concentrations affects yeast sexual development similarly to oxygen depletion.
- This effect is attributed to aspirin's anti-mitochondrial action.
Purpose of the Study:
- To investigate if other anti-inflammatory and anticancer drugs with known anti-mitochondrial activity affect yeast sexual development.
- To establish a yeast bio-assay for identifying drugs with anti-mitochondrial properties.
Main Methods:
- Utilized a unique yeast bio-assay with *Eremothecium ashbyi*.
- Monitored mitochondrion-dependent sexual structure development, riboflavin production, and hyphal morphology.
- Tested various anti-inflammatory (ibuprofen, indomethacin, salicylic acid, benzoic acid) and anticancer (Lonidamine) drugs.
Main Results:
- Multiple drugs, including ibuprofen, indomethacin, salicylic acid, benzoic acid, and Lonidamine, mimicked oxygen limitation effects on yeast.
- These drugs inhibited sexual structure development, reduced riboflavin production, and caused characteristic wrinkled/granular hyphae.
- The observed morphological pattern in yeast was specific to drugs with anti-mitochondrial activity.
Conclusions:
- The yeast bio-assay effectively identifies drugs with anti-mitochondrial actions.
- This assay can be applied to screen for novel drugs with anti-mitochondrial properties from diverse sources.
- Yeast sexual development serves as a sensitive indicator for mitochondrial inhibition by various compounds.
