Farnesol-Induced Cell Death and Stimulation of 3-Hydroxy-3-Methylglutaryl-Coenzyme A Reductase Activity in Tobacco cv Bright Yellow-2 Cells,

Hemmerlin, Andréa; Bach, Thomas J.

doi:10.1104/pp.123.4.1257

Cited by 65 publications

(55 citation statements)

References 70 publications

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“…The concomitant modulation of the activity of the MVA and MEP pathways is a subject of extensive studies; the rate of precursor exchange may reach 100% and 80% from the plastids to the cytoplasm and vice versa (Hemmerlin and Bach, 2000;Schuhr et al, 2003), although these values were observed upon inhibitor treatment. Various intermediates (e.g.…”

Section: Discussionmentioning

confidence: 99%

Modeling of Dolichol Mass Spectra Isotopic Envelopes as a Tool to Monitor Isoprenoid Biosynthesis

et al. 2017

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The cooperation of the mevalonate (MVA) and methylerythritol phosphate (MEP) pathways, operating in parallel in plants to generate isoprenoid precursors, has been studied extensively. Elucidation of the isoprenoid metabolic pathways is indispensable for the rational design of plant and microbial systems for the production of industrially valuable terpenoids. Here, we describe a new method, based on numerical modeling of mass spectra of metabolically labeled dolichols (Dols), designed to quantitatively follow the cooperation of MVA and MEP reprogrammed upon osmotic stress (sorbitol treatment) in Arabidopsis (Arabidopsis thaliana). The contribution of the MEP pathway increased significantly (reaching 100%) exclusively for the dominating Dols, while for long-chain Dols, the relative input of the MEP and MVA pathways remained unchanged, suggesting divergent sites of synthesis for dominating and long-chain Dols. The analysis of numerically modeled Dol mass spectra is a novel method to follow modulation of the concomitant activity of isoprenoid-generating pathways in plant cells; additionally, it suggests an exchange of isoprenoid intermediates between plastids and peroxisomes.Isopentenyl diphosphate (IPP), the building block of isoprenoids, the most numerous class of secondary metabolites, is derived in plants from two pathways operating in parallel: the cytoplasmic mevalonate (MVA) and the plastidic methylerythritol phosphate (MEP) pathways (Rohmer, 1999;Pulido et al., 2012).Analysis of over 130 isoprenoids has shown that, in angiosperms under standard growth conditions, carotenoids and chlorophyll phytyl chains on the one hand and phytosterols on the other are made nearly exclusively via a single pathway (MEP and MVA, respectively), while numerous other isoprenoids, including dolichols (Dols; Skorupinska-Tudek et al., 2008), are of mixed origin (Hemmerlin et al., 2012).The cooperation of the two pathways (often called cross talk) is considered essential for plant adaptive responses to biotic and abiotic stresses. Consequently, their relative contributions to the formation of IPP are modulated, and the expression of particular genes of the MVA and MEP pathways is frequently correlated with stress (pathogen attack, elicitation, wounding, etc.;Hemmerlin et al., 2012) or plant development (Opitz et al., 2014). Interestingly, the effect of stress on the regulation of the MEP-MVA balance has so far been analyzed only qualitatively.Several methodologies have been employed to unravel the relative contributions of the MVA and MEP pathways to isoprenoids, such as metabolic labeling with isotopically labeled precursors (stable isotopes or radioisotopes were used), followed by structural analysis of the product of interest or blockage of the pathway (chemical, with pathway-specific inhibitors, or genetic), followed by quantification of the isoprenoid intermediates and/or end products. The advantages

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Section: Discussionmentioning

confidence: 99%

Modeling of Dolichol Mass Spectra Isotopic Envelopes as a Tool to Monitor Isoprenoid Biosynthesis

et al. 2017

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“…By inhibiting HMG-CoA reductase, mevinolin blocks the accumulation of the five-carbon precursor mevalonic acid, which is used to generate long chain prenyl moieties by successive condensation reactions (54). Prior studies confirmed that mevinolin is effective in plant suspension cultures and will reduce the availability of farnesyl and geranylgeranyl pyrophosphate in vivo (35,55). Following transfection, the protoplasts FIGURE 5.…”

Section: Mub Proteins Can Be Prenylated In Vitro-mentioning

confidence: 99%

MUBs, a Family of Ubiquitin-fold Proteins That Are Plasma Membrane-anchored by Prenylation

Downes

Saracco

Lee

et al. 2006

Journal of Biological Chemistry

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Ubiquitin (Ub)-fold proteins are rapidly emerging as an important class of eukaryotic modifiers, which often exert their influence by post-translational addition to other intracellular proteins. Despite assuming a common ␤-grasp threedimensional structure, their functions are highly diverse because of distinct surface features and targets and include tagging proteins for selective breakdown, nuclear import, autophagic recycling, vesicular trafficking, polarized morphogenesis, and the stress response. Here we describe a novel family of Membrane-anchored Ub-fold (MUB) proteins that are present in animals, filamentous fungi, and plants. Extending from the C terminus of the Ub-fold is typically a cysteinecontaining CAAX (where A indicates aliphatic amino acid) sequence that can direct the attachment of either a 15-carbon farnesyl or a 20-carbon geranylgeranyl moiety in vitro. Modified forms of several MUBs were detected in transgenic Arabidopsis thaliana, suggesting that these MUBs are prenylated in vivo. Both cell fractionation and confocal microscopic analyses of Arabidopsis plants expressing GFP-MUB fusions showed that the modified forms are membrane-anchored with a significant enrichment on the plasma membrane. This plasma membrane location was blocked in vivo in prenyltransferase mutants and by mevinolin, which inhibits the synthesis of prenyl groups. In addition to the five MUBs with CAAX boxes, Arabidopsis has one MUB variant with a cysteine-rich C terminus distinct from the CAAX box that is also membrane-anchored, possibly through the attachment of a long chain acyl group. Although the physiological role(s) of MUBs remain unknown, the discovery of these prenylated forms further expands the diversity and potential functions of Ub-fold proteins in eukaryotic biology.The superfamily of ubiquitin (Ub) 4 -type proteins has emerged over the last decade as an influential set of post-translational modifiers in eukaryotes. These small proteins (ϳ75-180 amino acids) contain a signature ␤-grasp (or Ub-fold) core domain, created by an ␣-helix transversing a groove created by an arched four-strand ␤-sheet (1). Extending from the core is a short flexible C-terminal extension that enables their attachment to other molecules through the terminal carboxyl group. The first and best-known member of this family is Ub (2, 3). It functions by becoming ligated to other proteins through an isopeptide bond between the C-terminal glycine of Ub and free lysine ⑀-amino groups in the target. The main role of Ub is to direct selective proteolysis by assembling chains of Ub monomers linked internally through Lys-48 onto various target proteins to promote their recognition by the 26 S proteasome. Others include roles in DNA repair via attachment of Lys-63-linked chains and endomembrane trafficking, transcription, and chromatin remodeling via attachment of Ub monomers (2, 3).Since the discovery of Ub, a number of related modifiers have been found, including Related to Ub-1 (RUB1 or NEDD8), Small-Ub-like Modifier (SUMO), Autophagy (ATG)-8 an...

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“…26 Farnesol-induced apoptosis has also been reported in tobacco cells. 27 In addition, farnesol has recently been found to be a potent and selective inhibitor of one class of monoamine oxidases (MAO-B). 28 The family of heterocyclic farnesol analogs described above now provides a tool to discriminate between yeast-hyphal quorum sensing and pathogenicity.…”

Section: Discussionmentioning

confidence: 99%

Influence of heterocyclic and oxime-containing farnesol analogs on quorum sensing and pathogenicity in Candida albicans

Shchepin

Navarathna

Dumitru

et al. 2008

Bioorganic & Medicinal Chemistry

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Farnesol-Induced Cell Death and Stimulation of 3-Hydroxy-3-Methylglutaryl-Coenzyme A Reductase Activity in Tobacco cv Bright Yellow-2 Cells,

Cited by 65 publications

References 70 publications

Modeling of Dolichol Mass Spectra Isotopic Envelopes as a Tool to Monitor Isoprenoid Biosynthesis

Modeling of Dolichol Mass Spectra Isotopic Envelopes as a Tool to Monitor Isoprenoid Biosynthesis

MUBs, a Family of Ubiquitin-fold Proteins That Are Plasma Membrane-anchored by Prenylation

Influence of heterocyclic and oxime-containing farnesol analogs on quorum sensing and pathogenicity in Candida albicans

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