Dataset Information

Lactate dehydrogenase and glycerol-3-phosphate dehydrogenase cooperatively regulate growth and carbohydrate metabolism during Drosophila melanogaster larval development.

ABSTRACT: The dramatic growth that occurs during Drosophila larval development requires rapid conversion of nutrients into biomass. Many larval tissues respond to these biosynthetic demands by increasing carbohydrate metabolism and lactate dehydrogenase (LDH) activity. The resulting metabolic program is ideally suited for synthesis of macromolecules and mimics the manner by which cancer cells rely on aerobic glycolysis. To explore the potential role of Drosophila LDH in promoting biosynthesis, we examined how Ldh mutations influence larval development. Our studies unexpectedly found that Ldh mutants grow at a normal rate, indicating that LDH is dispensable for larval biomass production. However, subsequent metabolomic analyses suggested that Ldh mutants compensate for the inability to produce lactate by generating excess glycerol-3-phosphate (G3P), the production of which also influences larval redox balance. Consistent with this possibility, larvae lacking both LDH and G3P dehydrogenase (GPDH1) exhibit growth defects, synthetic lethality and decreased glycolytic flux. Considering that human cells also generate G3P upon inhibition of lactate dehydrogenase A (LDHA), our findings hint at a conserved mechanism in which the coordinate regulation of lactate and G3P synthesis imparts metabolic robustness to growing animal tissues.

SUBMITTER: Li H

PROVIDER: S-EPMC6765128 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

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Lactate dehydrogenase and glycerol-3-phosphate dehydrogenase cooperatively regulate growth and carbohydrate metabolism during Drosophila melanogaster larval development.

Li Hongde H Rai Madhulika M Buddika Kasun K Sterrett Maria C MC Luhur Arthur A Mahmoudzadeh Nader H NH Julick Cole R CR Pletcher Rose C RC Chawla Geetanjali G Gosney Chelsea J CJ Burton Anna K AK Karty Jonathan A JA Montooth Kristi L KL Sokol Nicholas S NS Tennessen Jason M JM

Development (Cambridge, England) 20190912 17

The dramatic growth that occurs during Drosophila larval development requires rapid conversion of nutrients into biomass. Many larval tissues respond to these biosynthetic demands by increasing carbohydrate metabolism and lactate dehydrogenase (LDH) activity. The resulting metabolic program is ideally suited for synthesis of macromolecules and mimics the manner by which cancer cells rely on aerobic glycolysis. To explore the potential role of Drosophila LDH in promoting biosynthesi ...[more]

PMID: 31399469

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Project description:Microorganisms play a central role in the biology of vinegar flies such as Drosophila suzukii and Drosophila melanogaster: serving as a food source to both adults and larvae, and influencing a range of traits including nutrition, behavior, and development. The niches utilized by the fly species partially overlap, as do the microbiota that sustain them, and interactions among these players may drive the development of crop diseases. To learn more about how the microbiota of one species may affect the other, we isolated and identified microbes from field-caught D. suzukii, and then characterized their effects on D. melanogaster larval development time in the laboratory. We found that the D. suzukii microbiota consistently included both yeasts and bacteria. It was dominated by yeasts of the genus Hanseniaspora, and bacteria from the families Acetobacteraceae and Enterobacteriaceae. Raising D. melanogaster under gnotobiotic conditions with each microbial isolate individually, we found that some bacteria promoted larval development relative to axenic conditions, but most did not have a significant effect. In contrast, nearly all the yeasts tested significantly accelerated larval development. The one exception was Starmerella bacillaris, which had the opposite effect: significantly slowing larval developmental rate. We investigated the basis for this effect by examining whether S. bacillaris cells could sustain larval growth, and measuring the survival of S. bacillaris and other yeasts in the larval gut. Our results suggest S. bacillaris is not digested by D. melanogaster and therefore cannot serve as a source of nutrition. These findings have interesting implications for possible interactions between the two Drosophilia species and their microbiota in nature. Overall, we found that microbes isolated from D. suzukii promote D. melanogaster larval development, which is consistent with the model that infestation of fruit by D. suzukii can open up habitat for D. melanogaster. We propose that the microbiome is an important dimension of the ecological interactions between Drosophila species.

Dataset Information

Lactate dehydrogenase and glycerol-3-phosphate dehydrogenase cooperatively regulate growth and carbohydrate metabolism during Drosophila melanogaster larval development.

Publications

Lactate dehydrogenase and glycerol-3-phosphate dehydrogenase cooperatively regulate growth and carbohydrate metabolism during <i>Drosophila melanogaster</i> larval development.

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