title: Molecular characterization of propolis-induced cell death in Saccharomyces cerevisiae.
abstract: Propolis, a natural product of plant resins, is used by the bees to seal holes in their honeycombs and protect the hive entrance. However, propolis has also been used in folk medicine for centuries. Here, we apply the power of Saccharomyces cerevisiae as a model organism for studies of genetics, cell biology, and genomics to determine how propolis affects fungi at the cellular level. Propolis is able to induce an apoptosis cell death response. However, increased exposure to propolis provides a corresponding increase in the necrosis response. We showed that cytochrome c but not endonuclease G (Nuc1p) is involved in propolis-mediated cell death in S. cerevisiae. We also observed that the metacaspase YCA1 gene is important for propolis-mediated cell death. To elucidate the gene functions that may be required for propolis sensitivity in eukaryotes, the full collection of about 4,800 haploid S. cerevisiae deletion strains was screened for propolis sensitivity. We were able to identify 138 deletion strains that have different degrees of propolis sensitivity compared to the corresponding wild-type strains. Systems biology revealed enrichment for genes involved in the mitochondrial electron transport chain, vacuolar acidification, negative regulation of transcription from RNA polymerase II promoter, regulation of macroautophagy associated with protein targeting to vacuoles, and cellular response to starvation. Validation studies indicated that propolis sensitivity is dependent on the mitochondrial function and that vacuolar acidification and autophagy are important for yeast cell death caused by propolis.
authors.affiliation: Departamento de Ciências Farmacêuticas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Avenida do Café S/N, Ribeirão Preto, São Paulo, Brazil.
authors.forename: Patrícia Alves
authors.initials: PA
authors.lastname: de Castro
authors.forename: Marcela
authors.initials: M
authors.lastname: Savoldi
authors.forename: Diego
authors.initials: D
authors.lastname: Bonatto
authors.forename: Mário Henrique
authors.initials: MH
authors.lastname: Barros
authors.forename: Maria Helena S
authors.initials: MH
authors.lastname: Goldman
authors.forename: Andresa A
authors.initials: AA
authors.lastname: Berretta
authors.forename: Gustavo Henrique
authors.initials: GH
authors.lastname: Goldman
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D015966:Gene Expression Regulation, Fungal / Q000187:drug effects*; D008928:Mitochondria / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D011429:Propolis / Q000494:pharmacology*; D012441:Saccharomyces cerevisiae / Q000166:cytology* / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D029701:Saccharomyces cerevisiae Proteins; D011429:Propolis