ArticlePlant physiology2002
Inhibition of squalene synthase and squalene epoxidase in tobacco cells triggers an up-regulation of 3-hydroxy-3-methylglutaryl coenzyme a reductase.
Article in Plant physiology, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers.
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Who cites it
57 citing papers in PubMed, 144 citations in OpenAlex.
- The potential of metabolic engineering for sustainable phytosterol production.Advanced biotechnology · 2026Review
- Rab geranylgeranyl transferase activity is required for proper sterol biosynthesis in Arabidopsis thaliana.Plant & cell physiology · 2026Article
- Sterols in plant biologyCell surface (Amsterdam, Netherlands) · 2025Review
- Uncovering the Hidden Potential of Phytoene Production by the FungusFoods (Basel, Switzerland) · 2024Article
- Methyl-Jasmonate Functions as a Molecular Switch Promoting Cross-Talk between Pathways for the Biosynthesis of Isoprenoid Backbones Used to Modify Proteins in Plants.Plants (Basel, Switzerland) · 2024Article
- Transcriptomic and physiological analysis of atractylodes chinensis in response to drought stress reveals the putative genes related to sesquiterpenoid biosynthesis.BMC plant biology · 2024Article
- Reduced Survival and Resistance of Rhodotorula mucilaginosa Following Inhibition of Pigment Production by Naftifine.Current microbiology · 2023Article
- Heterologous expression of Chlorophytum borivilianum Squalene epoxidase in tobacco modulates stigmasterol production and alters vegetative and reproductive growth.Plant cell reports · 2023Article
- Molecular characterization and transcriptional regulation analysis of theFrontiers in plant science · 2023Article
- Elucidation of sterol biosynthesis pathway and its co-regulation with fatty acid biosynthesis in the oleaginous marine protistFrontiers in bioengineering and biotechnology · 2023Article
- Genes and Regulatory Mechanisms for Ginsenoside Biosynthesis.Journal of plant biology = Singmul Hakhoe chi · 2023Review
- Downregulation of Squalene Synthase Broadly Impacts Isoprenoid Biosynthesis in Guayule.Metabolites · 2022Article
- Effects of impaired steryl ester biosynthesis on tomato growth and developmental processes.Frontiers in plant science · 2022Article
- Article
- Green Microalgae Strain Improvement for the Production of Sterols and Squalene.Plants (Basel, Switzerland) · 2021Article
- Comparative transcriptome analysis reveals sesquiterpenoid biosynthesis among 1-, 2- and 3-year old Atractylodes chinensis.BMC plant biology · 2021Article
- Expressional diversity of grapevine 3-Hydroxy-3-methylglutaryl-CoA reductase (VvHMGR) in different grapes genotypes.BMC plant biology · 2021Article
- Article
- Effects of moderate high temperature and UV-B on accumulation of withanolides and relative expression of the squalene synthase gene in Physalis peruviana.Turkish journal of biology = Turk biyoloji dergisi · 2020Article
- Melatonin-Induced Transcriptome Variation of Rapeseed Seedlings under Salt Stress.International journal of molecular sciences · 2019Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
To get some insight into the regulatory mechanisms controlling the sterol branch of the mevalonate pathway, tobacco (Nicotiana tabacum cv Bright Yellow-2) cell suspensions were treated with squalestatin-1 and terbinafine, two specific inhibitors of squalene synthase (SQS) and squalene epoxidase, respectively. These two enzymes catalyze the first two steps involved in sterol biosynthesis. In highly dividing cells, SQS was actively expressed concomitantly with 3-hydroxy-3-methylglutaryl coenzyme A reductase and both sterol methyltransferases. At nanomolar concentrations, squalestatin was found to inhibit efficiently sterol biosynthesis as attested by the rapid decrease in SQS activity and [(14)C]radioactivity from acetate incorporated into sterols. A parallel dose-dependent accumulation of farnesol, the dephosphorylated form of the SQS substrate, was observed without affecting farnesyl diphosphate synthase steady-state mRNA levels. Treatment of tobacco cells with terbinafine is also shown to inhibit sterol synthesis. In addition, this inhibitor induced an impressive accumulation of squalene and a dose-dependent stimulation of the triacylglycerol content and synthesis, suggesting the occurrence of regulatory relationships between sterol and triacylglycerol biosynthetic pathways. We demonstrate that squalene was stored in cytosolic lipid particles, but could be redirected toward sterol synthesis if required. Inhibition of either SQS or squalene epoxidase was found to trigger a severalfold increase in enzyme activity of 3-hydroxy-3-methylglutaryl coenzyme A reductase, giving first evidence for a positive feedback regulation of this key enzyme in response to a selective depletion of endogenous sterols. At the same time, no compensatory responses mediated by SQS were observed, in sharp contrast to the situation in mammalian cells.
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