Introduction

In a fruitful collaboration with Dr. Jason Tennessen’s lab at Indiana University, we uncovered an exciting cooperative interaction between lactate dehydrogenase (LDH) and glycerol-3-phosphate dehydrogenase (GPDH1) to regulate proper larval redox balance. Here is the abstract of the manuscript:

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.

Further Reading

If you are interested, please read the full story that is freely available here.

Cite this work

Li H, Rai M, Buddika K, Sterrett MC, Luhur A, Mahmoudzadeh NH, Julick CR, Pletcher RC, Chawla G, Gosney CJ, Burton AK, Karty JA, Montooth KL, Sokol NS, Tennessen JM. Lactate dehydrogenase and glycerol-3-phosphate dehydrogenase cooperatively regulate growth and carbohydrate metabolism during Drosophila melanogaster larval development. Development. 2019 Sep 12;146(17):dev175315. doi: 10.1242/dev.175315. PMID: 31399469; PMCID: PMC6765128.