THE α-GLYCEROPHOSPHATE CYCLE IN DROSOPHILA MELANOGASTER

Abstract

"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.