Substitution of cellular fatty acids in yeast cells by the antibiotic cerulenin and exogenous fatty acids

Awaya, Juichi; Ohno, Tadao; Ohno, Hiroie; Ōmura, Satoshi

doi:10.1016/0005-2760(75)90022-3

Cited by 51 publications

(37 citation statements)

References 11 publications

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“…Fatty acid metabolism involves Cytb5-dependent reactions. We tested whether irc21Δ cells were sensitive to overall dampening of fatty acid production by cerulenin, an inhibitor of fatty acid synthase (FAS) that prevents the synthesis of medium- and long-chain fatty acids (MCFAs and LCFAs, respectively) and of very-LCFAs (VLCFAs) (Awaya et al., 1975). irc21 mutants were hypersensitive to cerulenin (Figure 2D), implying that Irc21 may affect fatty acid metabolism.…”

Section: Resultsmentioning

confidence: 99%

PP2A Controls Genome Integrity by Integrating Nutrient-Sensing and Metabolic Pathways with the DNA Damage Response

et al. 2017

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SummaryMec1ATR mediates the DNA damage response (DDR), integrating chromosomal signals and mechanical stimuli. We show that the PP2A phosphatases, ceramide-activated enzymes, couple cell metabolism with the DDR. Using genomic screens, metabolic analysis, and genetic and pharmacological studies, we found that PP2A attenuates the DDR and that three metabolic circuits influence the DDR by modulating PP2A activity. Irc21, a putative cytochrome b5 reductase that promotes the condensation reaction generating dihydroceramides (DHCs), and Ppm1, a PP2A methyltransferase, counteract the DDR by activating PP2A; conversely, the nutrient-sensing TORC1-Tap42 axis sustains DDR activation by inhibiting PP2A. Loss-of-function mutations in IRC21, PPM1, and PP2A and hyperactive tap42 alleles rescue mec1 mutants. Ceramides synergize with rapamycin, a TORC1 inhibitor, in counteracting the DDR. Hence, PP2A integrates nutrient-sensing and metabolic pathways to attenuate the Mec1ATR response. Our observations imply that metabolic changes affect genome integrity and may help with exploiting therapeutic options and repositioning known drugs.

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Section: Resultsmentioning

confidence: 99%

PP2A Controls Genome Integrity by Integrating Nutrient-Sensing and Metabolic Pathways with the DNA Damage Response

et al. 2017

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“…Nieman (1954) has proposed such a mode of action for the bacteriostatic properties of fatty acids, and Awaya et al (1975) have offered a similar explanation concerning the toxic effects of C12 and C,3 free fatty acids on a strain of Saccharomyces cerevisiae . and Okamoto, Katoh & Murakami (1977) have shown There is also evidence that unsaturated fatty acids act as inhibitors of the Hill reaction or as uncouplers of photophosphorylation .…”

Section: Discussionmentioning

confidence: 96%

A chemical characterization of an algal inhibitor obtained from chlamydomonas

McCracken

Middaugh

1980

Hydrobiologia

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This investigation was conducted to characterize the algal inhibitory material originally isolated by Proctor (1957b) from Chlamydomonas. Analysis of purified extracts demonstrated that the inhibitor was a mixture of fatty acids . The identity and relative percentages of most of the components of the mixture were determined by GLC analysis . There is evidence that unsaturated fatty acids were responsible for the majority of the toxicity .

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“…To test this hypothesis, detached 3-week-old leaf blades not yet showing lesions in the transgenic lines were treated with 200 mM 18:2 in the presence or absence of 5 mM cerulenin, a specific inhibitor of KAS I and KAS II, which are key enzymes of de novo FA biosynthesis (Awaya et al, 1975;Packter and Stumpf, 1975;Koo et al, 2005). The extent of cell death was evaluated by electrolyte leakage measurements.…”

Section: Inhibition Of Fa Biosynthesis Decreases 18:2-induced Cell Dementioning

confidence: 99%

Ectopic expression of WRI1 affects fatty acid homeostasis in Brachypodium distachyon vegetative tissues

et al. 2015

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Triacylglycerol (TAG) is a storage lipid used for food purposes and as a renewable feedstock for biodiesel production. WRINKLED1 (WRI1) is a transcription factor that governs fatty acid (FA) synthesis and, indirectly, TAG accumulation in oil-storing plant tissues, and its ectopic expression has led to TAG accumulation in vegetative tissues of different dicotyledonous plants. The ectopic expression of BdWRI1 in the grass Brachypodium distachyon induced the transcription of predicted genes involved in glycolysis and FA biosynthesis, and TAG content was increased up to 32.5-fold in 8-week-old leaf blades. However, the ectopic expression of BdWRI1 also caused cell death in leaves, which has not been observed previously in dicotyledonous plants such as Arabidopsis (Arabidopsis thaliana). Lipid analysis indicated that the free FA content was 2-fold elevated in BdWRI1-expressing leaf blades of B. distachyon. The transcription of predicted genes involved in b-oxidation was induced. In addition, linoleic FA treatment caused cell death in B. distachyon leaf blades, an effect that was reversed by the addition of the FA biosynthesis inhibitor cerulenin. Taken together, ectopic expression of BdWRI1 in B. distachyon enhances FA biosynthesis and TAG accumulation in leaves, as expected, but also leads to increased free FA content, which has cytotoxic effects leading to cell death. Thus, while WRI appears to ubiquitously affect FA biosynthesis and TAG accumulation in diverse plants, its ectopic expression can lead to undesired side effects depending on the context of the specific lipid metabolism of the respective plant species.

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Substitution of cellular fatty acids in yeast cells by the antibiotic cerulenin and exogenous fatty acids

Cited by 51 publications

References 11 publications

PP2A Controls Genome Integrity by Integrating Nutrient-Sensing and Metabolic Pathways with the DNA Damage Response

PP2A Controls Genome Integrity by Integrating Nutrient-Sensing and Metabolic Pathways with the DNA Damage Response

A chemical characterization of an algal inhibitor obtained from chlamydomonas

Ectopic expression of WRI1 affects fatty acid homeostasis in Brachypodium distachyon vegetative tissues

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