Arabidopsis 3-hydroxy-3-methylglutaryl-CoA reductase is regulated at the post-translational level in response to alterations of the sphingolipid and the sterol biosynthetic pathways

Nieto, Benjamín; Forés, Oriol; Arró, Montserrat; Ferrer, Albert

doi:10.1016/j.phytochem.2008.10.010

Cited by 53 publications

(48 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We found that HMGR activity was decreased in 35S:ADS plants treated with terbinafine, which conflicts with the results of other studies; HMGR activity was increased in tobacco BY-2 cells and Arabidopsis treated with terbinafine (Nieto et al 2009;Wentzinger et al 2002). Differences in growth conditions and terbinafine treatment may affect gene expression and enzyme activity of HMGR.…”

contrasting

confidence: 99%

See 1 more Smart Citation

Platform for “Chemical Metabolic Switching” to Increase Sesquiterpene Content in Plants

Kobayashi

Yamaguchi

et al. 2017

Plant Biotechnology

View full text Add to dashboard Cite

The biosynthetic pathway of cytosolic isoprenoids bifurcates after farnesyl diphosphate into sesquiterpene and triterpene pathways. "Metabolic switching" has been used to increase sesquiterpene content in plants by suppressing the competitive triterpene pathway using transgenic technology. To develop "metabolic switching" without using transgenic technology, we developed a model system of "chemical metabolic switching" using inhibitors of the competitive pathway. Arabidopsis plants that overexpress the amorpha-4,11-diene synthase gene were treated with squalestatin, a squalene synthase inhibitor, or terbinafine, a squalene epoxidase inhibitor. We then analyzed total sterol content as major triterpenes and amorpha-4,11-diene in the plant. Plants treated with squalestatin showed decreased total sterol content and increased amorpha-4,11-diene content. In contrast, plants treated with terbinafine showed decreased total sterol content, but amorpha-4,11-diene accumulation was quite low. These results suggest that inhibition of the enzyme just below the branch point is more effective than inhibition of enzymes far from the branch point for "chemical metabolic switching". In addition, the activity of 3-hydroxy-3-methylglutaryl-CoA reductase, the rate-limiting enzyme of the cytosolic isoprenoid biosynthetic pathway, was upregulated in plants treated with squalestatin, suggesting that feedback regulation of 3-hydroxy-3-methylglutaryl-CoA reductase may contribute to amorpha-4,11-diene production. Here we demonstrated the effectiveness of "chemical metabolic switching" in plants.

show abstract

contrasting

confidence: 99%

“…squalestatin and terbinafine treatment in Arabidopsis (Nieto et al 2009). To determine if HMGR was subjected to feedback regulation in our system, HMGR gene expression and enzyme activity were measured in 35S:ADS plants treated with inhibitors (supplemental information).…”

mentioning

confidence: 99%

Platform for “Chemical Metabolic Switching” to Increase Sesquiterpene Content in Plants

Kobayashi

Yamaguchi

et al. 2017

Plant Biotechnology

View full text Add to dashboard Cite

show abstract

“…Previous studies have shown that both the genetic and pharmacological block of the sterol biosynthesis pathway leads to a compensatory up-regulation of HMGR activity (Wentzinger et al, 2002;Babiychuk et al, 2008;Nieto et al, 2009;Posé et al, 2009;Closa et al, 2010). In agreement with these observations, HMGR activity also was enhanced in FPS-silenced plants (Fig.…”

Section: Down-regulation Of Fps Activity In Arabidopsis Amirna-based supporting

confidence: 88%

“…Recent reports have shown that a selective blockage of the sterol pathway triggers a positive feedback regulatory response of HMGR, the main regulatory enzyme of the MVA pathway (Wentzinger et al, 2002;Babiychuk et al, 2008;Nieto et al, 2009;Posé et al, 2009). Such a regulatory response also has been reported in Arabidopsis seeds with reduced levels of FPS activity (Closa et al, 2010;Keim et al, 2012).…”

Section: Down-regulation Of Fps Leads To Altered Levels Of Major Mva-mentioning

confidence: 79%

“…Quantitative analysis of ubiquinones using ultra-performance liquid chromatography-mass spectrometry showed that the levels of the major ubiquinone species (UQ-9) were decreased by 30% in silenced amiFPSa and amiFPSb plants compared with EV plants grown on medium supplemented with MFZ, whereas the levels of UQ-10, a minor ubiquinone species in Arabidopsis, were increased drastically by 3 and 4 times, respectively (Fig. 3C).Recent reports have shown that a selective blockage of the sterol pathway triggers a positive feedback regulatory response of HMGR, the main regulatory enzyme of the MVA pathway (Wentzinger et al, 2002;Babiychuk et al, 2008;Nieto et al, 2009;Posé et al, 2009). Such a regulatory response also has been reported in Arabidopsis seeds with reduced levels of FPS activity (Closa et al, 2010;Keim et al, 2012).…”

mentioning

confidence: 85%

See 1 more Smart Citation

Suppressing Farnesyl Diphosphate Synthase Alters Chloroplast Development and Triggers Sterol-Dependent Induction of Jasmonate- and Fe-Related Responses

et al. 2016

Self Cite

View full text Add to dashboard Cite

Farnesyl diphosphate synthase (FPS) catalyzes the synthesis of farnesyl diphosphate from isopentenyl diphosphate and dimethylallyl diphosphate. Arabidopsis (Arabidopsis thaliana) contains two genes (FPS1 and FPS2) encoding FPS. Single fps1 and fps2 knockout mutants are phenotypically indistinguishable from wild-type plants, while fps1/fps2 double mutants are embryo lethal. To assess the effect of FPS down-regulation at postembryonic developmental stages, we generated Arabidopsis conditional knockdown mutants expressing artificial microRNAs devised to simultaneously silence both FPS genes. Induction of silencing from germination rapidly caused chlorosis and a strong developmental phenotype that led to seedling lethality. However, silencing of FPS after seed germination resulted in a slight developmental delay only, although leaves and cotyledons continued to show chlorosis and altered chloroplasts. Metabolomic analyses also revealed drastic changes in the profile of sterols, ubiquinones, and plastidial isoprenoids. RNA sequencing and reverse transcription-quantitative polymerase chain reaction transcriptomic analysis showed that a reduction in FPS activity levels triggers the misregulation of genes involved in biotic and abiotic stress responses, the most prominent one being the rapid induction of a set of genes related to the jasmonic acid pathway. Down-regulation of FPS also triggered an iron-deficiency transcriptional response that is consistent with the irondeficient phenotype observed in FPS-silenced plants. The specific inhibition of the sterol biosynthesis pathway by chemical and genetic blockage mimicked these transcriptional responses, indicating that sterol depletion is the primary cause of the observed alterations. Our results highlight the importance of sterol homeostasis for normal chloroplast development and function and reveal important clues about how isoprenoid and sterol metabolism is integrated within plant physiology and development.Isoprenoids are the largest class of all known natural products in living organisms, with tens of thousands of different compounds. In plants, isoprenoids perform essential biological functions, including maintenance of proper membrane structure and function (sterols), electron transport (ubiquinones and plastoquinones), posttranslational protein modification (dolichols serving as glycosylation cofactors and prenyl groups), photosynthesis (chlorophylls and carotenoids), and regulation of growth and development (abscisic acid, brassinosteroids, cytokinins, and GAs [Croteau et al., 2000] and strigolactones [Al-Babili and Bouwmeester, 2015]). A large number of isoprenoids also play prominent roles as mediators of interactions between plants and their environment, including a variety of defense responses against biotic and abiotic stresses (Tholl and Lee, 2011). In fact, there is hardly any aspect of plant growth, development, and reproduction not relying on isoprenoids or isoprenoid-derived compounds. In addition, many plant isoprenoids are of great economic importan...

show abstract

AKIN10, a representative Arabidopsis SNF1‐related protein kinase 1 (SnRK1), phosphorylates and downregulates plant HMG‐CoA reductase

et al. 2017

View full text Add to dashboard Cite

HMG-CoA reductase (HMGR) is a key enzyme in the mevalonate pathway for sterols and cytosolic isoprenoid production. Although HMGR kinases from spinach, barley, and cauliflower tissues have been strongly suggested as members of SNF1-related protein kinases 1 (SnRK1), the phosphorylation and inactivation of HMGR by plant SnRK1s has not been demonstrated. In this study, we elucidated that AKIN10, an Arabidopsis SnRK1, acts as an HMGR kinase. The recombinant AKIN10 phosphorylates and inactivates AtHMGR1S using recombinant GRIK1 as the AKIN10 activator. In contrast, AKIN10-GRIK1 fails to inactivate AtHMGR1S-S577A, suggesting that this is achieved through Ser577 phosphorylation. Moreover, phosphorylation is detected not only in AtHMGR1S but also in AtHMGR1S-S577A, suggesting the presence of a novel regulatory mechanism of plant HMGR.

show abstract

Arabidopsis 3-hydroxy-3-methylglutaryl-CoA reductase is regulated at the post-translational level in response to alterations of the sphingolipid and the sterol biosynthetic pathways

Cited by 53 publications

References 33 publications

Platform for “Chemical Metabolic Switching” to Increase Sesquiterpene Content in Plants

Platform for “Chemical Metabolic Switching” to Increase Sesquiterpene Content in Plants

Suppressing Farnesyl Diphosphate Synthase Alters Chloroplast Development and Triggers Sterol-Dependent Induction of Jasmonate- and Fe-Related Responses

AKIN10, a representative Arabidopsis SNF1‐related protein kinase 1 (SnRK1), phosphorylates and downregulates plant HMG‐CoA reductase

Contact Info

Product

Resources

About