ArticlePLoS genetics2013
Mondo/ChREBP-Mlx-regulated transcriptional network is essential for dietary sugar tolerance in Drosophila.
Article in PLoS genetics, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers.
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Who cites it
63 citing papers in PubMed, 108 citations in OpenAlex.
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- Transcriptional Control of Lipid Metabolism.Advances in experimental medicine and biology · 2026Review
- Lipid Metabolism in Relation to Carbohydrate Metabolism.Advances in experimental medicine and biology · 2026Review
- Insect Lipidomics: Advances, Applications, and Physiological Insights.Advances in experimental medicine and biology · 2026Review
- Preclinical research in obesity-associated metabolic diseases using in vitro, multicellular, and non-mammalian models.Journal of physiology and biochemistry · 2025Review
- Drosophila melanogaster as a model organism to investigate sex specific differences.Scientific reports · 2025Article
- MLX phosphorylation stabilizes the ChREBP-MLX heterotetramer on tandem E-boxes to control carbohydrate and lipid metabolism.Science advances · 2025Article
- MLX phosphorylation stabilizes the ChREBP-MLX heterotetramer on tandem E-boxes to control carbohydrate and lipid metabolism.bioRxiv : the preprint server for biology · 2024Article
- Domestication GeneInternational journal of molecular sciences · 2024Article
- The fat body cortical actin network regulateseLife · 2023Article
- Reducing ether lipids improves Drosophila overnutrition-associated pathophysiology phenotypes via a switch from lipid storage to beta-oxidation.Scientific reports · 2022Article
- The polyol pathway is an evolutionarily conserved system for sensing glucose uptake.PLoS biology · 2022Article
- Aryl hydrocarbon receptor and Krüppel like factor 10 mediate a transcriptional axis modulating immune homeostasis in mosquitoes.Scientific reports · 2022Article
- Genetic variation of macronutrient tolerance in Drosophila melanogaster.Nature communications · 2022Article
- A low-sugar diet enhances Drosophila body size in males and females via sex-specific mechanisms.Development (Cambridge, England) · 2022Article
- Review
- Metabolic gene regulation by Drosophila GATA transcription factor Grain.PLoS genetics · 2021Article
- The glucose-sensing transcription factor MLX balances metabolism and stress to suppress apoptosis and maintain spermatogenesis.PLoS biology · 2021Article
- Salmonella Typhimurium impairs glycolysis-mediated acidification of phagosomes to evade macrophage defense.PLoS pathogens · 2021Article
- Balancing energy expenditure and storage with growth and biosynthesis during Drosophila development.Developmental biology · 2021Review
3 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Sugars are important nutrients for many animals, but are also proposed to contribute to overnutrition-derived metabolic diseases in humans. Understanding the genetic factors governing dietary sugar tolerance therefore has profound biological and medical significance. Paralogous Mondo transcription factors ChREBP and MondoA, with their common binding partner Mlx, are key sensors of intracellular glucose flux in mammals. Here we report analysis of the in vivo function of Drosophila melanogaster Mlx and its binding partner Mondo (ChREBP) in respect to tolerance to dietary sugars. Larvae lacking mlx or having reduced mondo expression show strikingly reduced survival on a diet with moderate or high levels of sucrose, glucose, and fructose. mlx null mutants display widespread changes in lipid and phospholipid profiles, signs of amino acid catabolism, as well as strongly elevated circulating glucose levels. Systematic loss-of-function analysis of Mlx target genes reveals that circulating glucose levels and dietary sugar tolerance can be genetically uncoupled: Krüppel-like transcription factor Cabut and carbonyl detoxifying enzyme Aldehyde dehydrogenase type III are essential for dietary sugar tolerance, but display no influence on circulating glucose levels. On the other hand, Phosphofructokinase 2, a regulator of the glycolysis pathway, is needed for both dietary sugar tolerance and maintenance of circulating glucose homeostasis. Furthermore, we show evidence that fatty acid synthesis, which is a highly conserved Mondo-Mlx-regulated process, does not promote dietary sugar tolerance. In contrast, survival of larvae with reduced fatty acid synthase expression is sugar-dependent. Our data demonstrate that the transcriptional network regulated by Mondo-Mlx is a critical determinant of the healthful dietary spectrum allowing Drosophila to exploit sugar-rich nutrient sources.
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