The alpha-glycerophosphate cycle in Drosophila melanogaster. IV. Metabolic, ultrastructural, and adaptive consequences of alphaGpdh-l "null" mutations.
"Null" mutations previously isolated at the alphaGpdh-1 locus of Drosophila melanogaster, because of disruption of the energy-producing alpha-glycerophosphate cycle, severely restrict the flight ability and relative viability of affected individuals. Two "null" alleles, alphaGpdh-1(BO-1-4), and alphaGpdh-1(BO-1-5,) when made hemizygous with a deficiency of the alphaGpdh-1 locus, Df(2L)GdhA, were rendered homozygous by recombination with and selective elimination of the Df(2L)GdhA chromosome. After over 25 generations, a homozygous alphaGpdh-1(BO-1-4) stock regained the ability to fly despite the continued absence of measurable alphaGPDH activity. Inter se heterozygotes of three noncomplementing alphaGpdh-1 "null" alleles and the "adapted" alphaGpdh-1(BO-1-4) homozygotes were examined for metabolic enzymatic activities related to the energy-producing and pyridine nucleotide-regulating functions of the alpha-glycerophosphate cycle in Drosophila. The enzyme functions tested included glyceraldehyde-3-phosphate dehydrogenase, cytoplasmic and soluble malate dehydrogenase, lactate dehydrogenase, mitochondrial NADH oxidation, oxidative phosphorylation, and respiratory control with the substrates alpha-glycerophosphate, succinate, and pyruvate. These activities in any of the mutant genotypes in early adult life were indistinguishable from those in the wild type. There was, however, a premature deterioration and atrophy of the ultrastructural integrity of flight muscle sarcosomes observed by electron microscopy in the "null" mutants. These observations were correlated with a decrease in state 3 mitochondrial oxidation with alpha-glycerophosphate, succinate, and pyruvate, as well as with loss of respiratory control in adults as early as 2 wk after eclosion. Such observations, which normally are seen in aged dipterans, were accompanied by premature mortality of the mutant heterozygotes. The adapted alphaGpdh-1(BO-1-4) was identical with wild type in each of the aging characters with the single exception of lowered rates of mitochondrial oxidative phosphorylation.
D000220:Adaptation, Biological; D000375:Aging; D000483:Alleles; D000782:Aneuploidy; D002874:Chromosome Mapping; D004331:Drosophila melanogaster / Q000201:enzymology / Q000378:metabolism*; D005796:Genes; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000378:metabolism; D005993:Glycerolphosphate Dehydrogenase / Q000378:metabolism; D005994:Glycerophosphates / Q000378:metabolism*; D006579:Heterozygote; D006720:Homozygote; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008291:Malate Dehydrogenase / Q000378:metabolism; D008854:Microscopy, Electron; D008928:Mitochondria / Q000378:metabolism; D009132:Muscles / Q000648:ultrastructure; D009154:Mutation; D009247:NADH, NADPH Oxidoreductases / Q000378:metabolism; D010085:Oxidative Phosphorylation; D010641:Phenotype; D011392:Proline / Q000378:metabolism; D011773:Pyruvates / Q000378:metabolism
D005994:Glycerophosphates; D011773:Pyruvates; D011392:Proline; D005993:Glycerolphosphate Dehydrogenase; D007770:L-Lactate Dehydrogenase; D008291:Malate Dehydrogenase; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases; D009247:NADH, NADPH Oxidoreductases