THE α-GLYCEROPHOSPHATE CYCLE IN DROSOPHILA MELANOGASTER

Abstract

ABSTRACT"Null" mutations previously isolated at the aGpdh-1 locus of Drosophila rnelanogaster, because of disruption of the energy-producing a-glycerophosphate cycle, severely restrict the flight ability and relative viability of affected individuals.Two "null" alleles, aGpdh-18°-1-4, and otGpdh-1 ~°-~-5, when made hemizygous with a deficiency of the aGpdh-I locus, Df(2L)Gdh,4, were rendered homozygous by recombination with and selective elimination of the Dfl2L)GdhA chromosome. After over 25 generations, a homozygous aGpdh-1 ~°-1-4 stock regained the ability to fly despite the continued absence of measurable aGPDH activity. Inter se heterozygotes of three noncomplementing aGpdh-1 "null" alleles and the "adapted" aGpdh-1 B°-'-~ homozygotes were examined for metabolic enzymatic activities related to the energy-producing and pyridine nucleotide-regulating functions of the o~-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 a-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 a-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 aGpdh-I B°-14 was identical with wild type in each of the aging characters with the single exception of lowered rates of mitochondrial oxidative phosphorylation.

Triglyceride Pools, Flight and Activity Variation at the Gpdh Locus in Drosophila melanogaster

“…One issue was the well-established role of Gpdh in flight. Clearly, homozygous null flies of D9-2/D9-2 have low fertility, are very short lived (,5 days), and cannot fly, which is the description of the early nulls by O'Brien and Shimada (1974). It is clear that loss or near loss of GPDH has marked effects on fitness and it is likely that true null homozygous genotypes are lethal in nature.…”

Flight muscle function in Drosophila requires colocalization of glycolytic enzymes.

“…Mutations in Gpdh can result in flightlessness (O'Brien and Shimada, 1974;Kotarski et al, 1983), thereby providing a useful selectable phenotype. Gpdh can encode three protein isoforms, each produced through differential splicing of the transcript from the single Gpdh gene.…”

Annual variation of enzyme polymorphism in four natural populations ofDrosophila melanogaster occupying different niches

“…The most important function of et-glycerophosphate dehydrogenase in the metabolism of an adult fly is its function in the flight muscle, where it acts as the impulsor of electrons into the interior of mitochondria, producing energy for flight (O'Brien & Shimada, 1974). Esterase-6 is a non-specific hydrolase of esters (Danford & Beardmore, 1979).…”