Department of Biology, Indiana University, Bloomington, IN 47405, USA.
Department of Chemistry, Indiana University, Bloomington, IN 47405, USA.
G3 (Bethesda). 2022 Jul 29;12(8). doi: 10.1093/g3journal/jkac115.
As the fruit fly, Drosophila melanogaster, progresses from one life stage to the next, many of the enzymes that compose intermediary metabolism undergo substantial changes in both expression and activity. These predictable shifts in metabolic flux allow the fly meet stage-specific requirements for energy production and biosynthesis. In this regard, the enzyme glycerol-3-phosphate dehydrogenase 1 (GPDH1) has been the focus of biochemical genetics studies for several decades and, as a result, is one of the most well-characterized Drosophila enzymes. Among the findings of these earlier studies is that GPDH1 acts throughout the fly lifecycle to promote mitochondrial energy production and triglyceride accumulation while also serving a key role in maintaining redox balance. Here, we expand upon the known roles of GPDH1 during fly development by examining how depletion of both the maternal and zygotic pools of this enzyme influences development, metabolism, and viability. Our findings not only confirm previous observations that Gpdh1 mutants exhibit defects in larval development, lifespan, and fat storage but also reveal that GPDH1 serves essential roles in oogenesis and embryogenesis. Moreover, metabolomics analysis reveals that a Gpdh1 mutant stock maintained in a homozygous state exhibits larval metabolic defects that significantly differ from those observed in the F1 mutant generation. Overall, our findings highlight unappreciated roles for GPDH1 in early development and uncover previously undescribed metabolic adaptations that could allow flies to survive the loss of this key enzyme.
当果蝇从一个生命阶段发展到下一个生命阶段时，构成中间代谢的许多酶在表达和活性上都发生了很大的变化。这些代谢通量的可预测变化使果蝇能够满足特定阶段对能量生产和生物合成的要求。在这方面，酶甘油-3-磷酸脱氢酶 1（GPDH1）已经成为生化遗传学研究的焦点已有几十年了，因此，它是最被广泛研究的果蝇酶之一。这些早期研究的结果之一是，GPDH1 在整个果蝇生命周期中发挥作用，促进线粒体能量产生和甘油三酯积累，同时在维持氧化还原平衡方面也起着关键作用。在这里，我们通过检查耗尽这种酶的母源和合子池如何影响发育、代谢和生存能力，来扩展 GPDH1 在果蝇发育过程中的已知作用。我们的研究结果不仅证实了先前的观察结果，即 Gpdh1 突变体在幼虫发育、寿命和脂肪储存方面存在缺陷，还揭示了 GPDH1 在卵子发生和胚胎发生中具有重要作用。此外，代谢组学分析表明，在纯合状态下维持的 Gpdh1 突变株表现出幼虫代谢缺陷，与在 F1 突变体代中观察到的缺陷显著不同。总的来说，我们的研究结果强调了 GPDH1 在早期发育中的未被重视的作用，并揭示了以前未描述的代谢适应，这可能使果蝇能够在失去这种关键酶的情况下生存。
