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-3phosphate (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.

Organismal physiology emerges from metabolic pathways and structures that can vary across development and among individuals. Matoo, Julick, and Montooth found significant variation, both genetic and ontogenetic, in mitochondrial physiology in wild-type and mitochondrial-nuclear...

Genetic effects are often context dependent, with the same genotype differentially affecting phenotypes across environments, life stages, and sexes. We used an environmental manipulation designed to increase energy demand during development to investigate energy demand as a general physiological explanation for context‐dependent effects of mutations, particularly for those mutations that affect metabolism. We found that increasing the photoperiod during which Drosophila larvae are active during development phenocopies a temperature‐dependent developmental delay in a mitochondrial‐nuclear genotype with disrupted metabolism. This result indicates that the context‐dependent fitness effects of this genotype are not specific to the effects of temperature and may generally result from variation in energy demand. The effects of this genotype also differ across life stages and between the sexes. The mitochondrial‐nuclear genetic interaction disrupts metabolic rate in growing larvae, but not in adults, and compromises female, but not male, reproductive fitness. These patterns are consistent with a model where context‐dependent genotype‐phenotype relationships may generally arise from differences in energy demand experienced by individuals across environments, life stages, and sexes.

Maternal investment is likely to have direct effects on offspring survival. In oviparous animals whose embryos are exposed to the external environment, maternal provisioning of molecular factors like mRNAs and proteins may help embryos cope with sudden changes in the environment. Here, we sought to modify the maternal mRNA contribution to offspring embryos and test for maternal effects on acute thermal tolerance in early embryos of We drove overexpression of a small heat shock protein gene () in female ovaries and measured the effects of acute thermal stress on offspring embryonic survival and larval development. We report that overexpression of the gene in female ovaries produced offspring embryos with increased thermal tolerance. We also found that brief heat stress in the early embryonic stage (0-1 h old) caused decreased larval performance later in life (5-10 days old), as indexed by pupation height. Maternal overexpression of protected embryos against this heat-induced defect in larval performance. Our data demonstrate that transient products of single genes have large and lasting effects on whole-organism environmental tolerance. Further, our results suggest that maternal effects have a profound impact on offspring survival in the context of thermal variability.

Maternal investment is likely to have direct effects on offspring survival. In oviparous animals whose embryos are exposed to the external environment, maternal provisioning of molecular factors like mRNAs and proteins may help embryos cope with sudden changes in the environment. Here we sought to modify the maternal mRNA contribution to offspring embryos and test for maternal effects on acute thermal tolerance in early embryos of Drosophila melanogaster. We drove in vivo overexpression of a small heat shock protein gene (Hsp23) in female ovaries and measured the effects of acute thermal stress on offspring embryonic survival and larval development. We report that overexpression of the Hsp23 gene in female ovaries produced offspring embryos with increased thermal tolerance. We also found that brief heat stress in the early embryonic stage (0 to 1 hour-old) caused decreased larval performance later in life (5 to 10 days-old), as indexed by pupation height, as well as increased development time to pupation. Maternal overexpression of Hsp23 protected embryos against these heat-induced larval defects. Our data demonstrate that transient products of single genes have large and lasting effects on whole-organism environmental tolerance. Further, our results suggest that maternal effects have a profound impact on offspring survival in the context of thermal variability.SUMMARY STATEMENTA gene-specific maternal effect confers thermal tolerance to offspring embryos in the fruit fly Drosophila melanogaster.