The Drosophila melanogaster enzyme glycerol-3-phosphate dehydrogenase 1 is required for oogenesis, embryonic development, and amino acid homeostasis

Abstract

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 (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 loss of this key enzyme.

E2F regulation of the Phosphoglycerate kinase gene is functionally important in Drosophila development

“…Intriguingly, just like in the Pgk ΔE2F mutant animals, occasional degenerating early egg chambers (stage 8 and earlier) were previously described in the Dp and E2f1 mutants ( 51 ) raising the possibility that this aspect of the Dp mutant phenotype may be due to loss of E2F regulation on the Pgk gene. Interestingly, degenerating egg chambers have previously been associated with metabolic defects, including alteration in the TCA cycle intermediates ( 52 ), nutritional status ( 39 , 40 ), and lipid transport ( 53 ). Egg chambers can degenerate before investing energy into egg production, in particular vitellogenesis.…”

The binding sites of E2F transcription factor inDrosophilametabolic genes are functionally distinct

“…Intriguingly, just like in the Pgk ΔE2F mutant animals, occasional degenerating early egg chambers (stage 8 and earlier) were previously described in the Dp and E2f1 mutants (Royzman et al , 2002) raising the possibility that this aspect of Dp mutant phenotype may be due to loss of E2F regulation on Pgk gene. Interestingly, degenerating egg chambers has previously been associated with metabolic defects, including alteration in the TCA cycle intermediates (Rai et al , 2022), nutritional status (Drummond-Barbosa & Spradling, 2001; McCall, 2004) and lipid transport (Matsuoka et al , 2017). Egg chambers can degenerate before investing energy into egg production, in particular vitellogenesis.…”

Complex II ambiguities—FADH2 in the electron transfer system

“…As a consequence, the prosthetic group FADH 2 appears erroneously as the substrate of CII in the ETS linked to succinate oxidation. This error is widely propagated in publications found from 2001 to 2023 ( 4 , 23 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 , 73 , 74 , 75 , 76 , 77 , 78 , 79 , 80 , 81 , 82 , 83 , 84 , 85 , 86 , 87 , 88 , 89 , 90 , 91 , 92 , 93 , 94 , 95 , 96 , 97 , 98 , 99 , 100 , 101 , 102 , 103 , 104 , 105 , 106 , 107 , 108 , 109 , 110 , 111 , 112 , 113 , 114 , 115 …”

“… CII e-input errors Ref. NADH → NAD + + H + ( 45 , 97 , 99 ) FADH 2 → FAD ( 4 , 23 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 , 73 , 74 , 75 , 76 , 77 , 78 , 79 , 80 , 81 , 82 , 83 , 84 , 85 , 86 , 87 , 88 , 89 , 90 , 91 , 92 , 93 , ...…”

“…FADH 2 is depicted as (1) product and (2) substrate of Complex II by ( A ) ( 4 ), ( B ) ( 80 ), as in ref. ( 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 , 73 , 74 , 75 , 76 , 77 , 78 , 79 , 80 , 81 , 82 , 83 , 84 , 85 , 86 , 87 , 88 , 89 , 90 , 91 , 92 , 93 , 94 , 95 , 96 , 97 , 98 , 99 , 104 , 192 , 193 , 194 , 199 , 201 , 202 , 203 , 204 ,…”