Farnesol induces the transcriptional accumulation of the Aspergillus nidulans Apoptosis-Inducing Factor (AIF)-like mitochondrial oxidoreductase.
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.
Savoldi
Marcela
M
Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, São Paulo, Brazil.
Malavazi
Iran
I
Soriani
Frederico Marianetti
FM
Capellaro
José Luiz
JL
Kitamoto
Katsuhiko
K
da Silva Ferreira
Márcia Eliana
ME
Goldman
Maria Helena S
MH
Goldman
Gustavo Henrique
GH
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
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