Fredericamycin A affects mitochondrial inheritance and morphology in Saccharomyces cerevisiae.
Fredericamycin A (FMA) is an antibiotic product of Streptomyces griseus that exhibits modest antitumor activity in vivo and in vitro, but, its functions in vivo are poorly understood. We identified this compound as an inducer of G1 arrest in the yeast, Saccharomyces cerevisiae. FMA exhibits an IC50 of 24 nM towards the growth of a disruptant of multi-drug resistance genes, W303-MLC30, and its cytotoxicity is a function of the time of exposure as well as drug dose. Addition of 0.8 microM of FMA caused aggregation of mitochondria within 10 min of incubation and the drug induced petites at high frequency after 4 h of incubation. Rho(-) cells were about 20 times more resistant to FMA than isogenic rho(+) cells. Overexpression of topoisomerase I, a previously suggested target of the drug, did not alleviate the sensitivity of the cells to FMA or the aggregation of mitochondria. Our results suggest that mitochondria are the primary target site of FMA.
Imamura
Yuko
Y
Department of Molecular Biotechnology, Graduate School of Advanced Sciences of Matter, Hiroshima University, Japan.
Yukawa
Masashi
M
Kimura
Ken-ichi
K
Takahashi
Hidetoshi
H
Suzuki
Yoshihiro
Y
Ojika
Makoto
M
Sakagami
Youji
Y
Tsuchiya
Eiko
E
D002453:Cell Cycle / Q000187:drug effects; D004264:DNA Topoisomerases, Type I / Q000235:genetics; D004272:DNA, Mitochondrial / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D016193:G1 Phase; D007546:Isoquinolines / Q000494:pharmacology; D008928:Mitochondria / Q000187:drug effects* / Q000473:pathology; D009154:Mutation; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000187:drug effects*; D013141:Spiro Compounds / Q000494:pharmacology
D004272:DNA, Mitochondrial; D007546:Isoquinolines; D013141:Spiro Compounds; D004264:DNA Topoisomerases, Type I; C016660:fredericamycin A