Open AccessLactate dehydrogenase and glycerol-3-phosphate dehydrogenase cooperatively regulate growth and carbohydrate metabolism during Drosophila melanogaster larval development
Author(s) -
Hongde Li,
Madhulika Rai,
Kasun Buddika,
Maria C. Sterrett,
Arthur Luhur,
Nader H. Mahmoudzadeh,
Cole R. Julick,
Rose C. Pletcher,
Geetanjali Chawla,
Chelsea J. Gosney,
Anna K. Burton,
Jonathan A. Karty,
Kristi L. Montooth,
Nicholas S. Sokol,
Jason M. Tennessen
Publication year - 2019
Publication title -
development
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.754
H-Index - 325
eISSN - 1477-9129
pISSN - 0950-1991
DOI - 10.1242/dev.175315
Subject(s) - biology , lactate dehydrogenase , glycolysis , dehydrogenase , biochemistry , metabolism , drosophila melanogaster , carbohydrate metabolism , microbiology and biotechnology , enzyme , gene
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 (dLDH) activity. The resulting metabolic program is ideally suited to synthesize macromolecules and mimics the manner by which cancer cells rely on aerobic glycolysis. To explore the potential role of Drosophila dLDH in promoting biosynthesis, we examined how dLdh mutations influence larval development. Our studies unexpectantly found that dLdh mutants grow at a normal rate, indicating that dLDH is dispensable for larval biomass production. However, subsequent metabolomic analyses suggested that dLdh 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 dLDH and G3P dehydrogenase (GPDH1) exhibit growth defects, synthetic lethality, and decreased glycolytic flux. Considering that human cells also generate G3P upon Lactate Dehydrogenase A (LDHA) inhibition, our findings hint at a conserved mechanism in which the coordinate regulation of lactate and G3P synthesis imparts metabolic robustness upon growing animal tissues.