title: Farnesol induces the transcriptional accumulation of the Aspergillus nidulans Apoptosis-Inducing Factor (AIF)-like mitochondrial oxidoreductase.
abstract: Farnesol (FOH) is a non-sterol isoprenoid produced by dephosphorylation of farnesyl pyrophosphate, a catabolite of the cholesterol biosynthetic pathway. These isoprenoids inhibit proliferation and induce apoptosis. It has been shown previously that FOH triggers morphological features characteristic of apoptosis in the filamentous fungus Aspergillus nidulans. Here, we investigate which pathways are influenced through FOH by examining the transcriptional profile of A. nidulans exposed to this isoprenoid. We observed decreased mRNA abundance of several genes involved in RNA processing and modification, transcription, translation, ribosomal structure and biogenesis, amino acid transport and metabolism, and ergosterol biosynthesis. We also observed increased mRNA expression of genes encoding a number of mitochondrial proteins and characterized in detail one of them, the aifA, encoding the Apoptosis-Inducing Factor (AIF)-like mitochondrial oxidoreductase. The DeltaaifA mutant is more sensitive to FOH (about 8.0% and 0% survival when exposed to 10 and 100 microM FOH respectively) than the wild type (about 97% and 3% survival when exposed to 10 and 100 microM FOH respectively). These results suggest that AifA is possibly important for decreasing the effects of FOH and reactive oxygen species. Furthermore, we showed an involvement of autophagy and protein kinase C in A. nidulans FOH-induced apoptosis.
authors.affiliation: Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, São Paulo, Brazil.
authors.forename: Marcela
authors.initials: M
authors.lastname: Savoldi
authors.forename: Iran
authors.initials: I
authors.lastname: Malavazi
authors.forename: Frederico Marianetti
authors.initials: FM
authors.lastname: Soriani
authors.forename: José Luiz
authors.initials: JL
authors.lastname: Capellaro
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Kitamoto
authors.forename: Márcia Eliana
authors.initials: ME
authors.lastname: da Silva Ferreira
authors.forename: Maria Helena S
authors.initials: MH
authors.lastname: Goldman
authors.forename: Gustavo Henrique
authors.initials: GH
authors.lastname: Goldman
mesh_terms: D017209:Apoptosis; D051033:Apoptosis Inducing Factor / Q000235:genetics*; D001233:Aspergillus nidulans / Q000187:drug effects / Q000201:enzymology / Q000235:genetics*; D001343:Autophagy; D005204:Farnesol / Q000494:pharmacology*; D005656:Fungal Proteins / Q000235:genetics; D020869:Gene Expression Profiling; D015966:Gene Expression Regulation, Fungal; D008928:Mitochondria / Q000201:enzymology; D024101:Mitochondrial Proteins / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D018384:Oxidative Stress; D010088:Oxidoreductases / Q000235:genetics*; D011493:Protein Kinase C / Q000378:metabolism; D012331:RNA, Fungal / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D017382:Reactive Oxygen Species / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic
chemical_list: D051033:Apoptosis Inducing Factor; D005656:Fungal Proteins; D024101:Mitochondrial Proteins; D012331:RNA, Fungal; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D005204:Farnesol; D010088:Oxidoreductases; D011493:Protein Kinase C