The α-Glycerophosphate Cycle in Drosophila melanogaster IV. Metabolic, Ultrastructural, and Adaptive Consequences of αGpdh-1 "Null" Mutations

Authors

• Stephen J. O'Brien, National Cancer Institute, BethesdaFollow
• Yoshio Shimada, National Institute of Child Health and Human Development

ORCID

0000-0001-7353-8301

ResearcherID

N-1726-2015

Document Type

Article

Publication Title

Journal of Cell Biology

ISSN

0021-9525

Publication Date

12-1-1974

Abstract

"Null" mutations previously isolated at the αGpdh-1 locus of Drosophila melanogaster, because of disruption of the energy-producing α-glycerophosphate cycle, severely restrict the flight ability and relative viability of affected individuals. Two "null" alleles, αGpdh-1^BO-1-4, and αGpdh-1^BO-1-5, when made hemizygous with a deficiency of the αGpdh-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 αGpdh-1^BO-1-4stock regained the ability to fly despite the continued absence of measurable αGPDH activity. Inter se heterozygotes of three noncomplementing αGpdh-1 "null" alleles and the "adapted" αGpdh-1^BO-1-4 homozygotes were examined for metabolic enzymatic activities related to the energy-producing and pyridine nucleotide-regulating functions of the α-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 α-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 α-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 αGpdh-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.

DOI

10.1083/jcb.63.3.864

Volume

63

Issue

3

First Page

864

Last Page

882

Comments

© 1974 Rockefeller University Press

Additional Comments

National Institute of General Medical Science Research Fellowship #6-F02-GM-49-633-01

NSUWorks Citation

O'Brien, Stephen J. and Yoshio Shimada. 1974. "The α-Glycerophosphate Cycle in Drosophila melanogaster IV. Metabolic, Ultrastructural, and Adaptive Consequences of αGpdh-1 "Null" Mutations." Journal of Cell Biology 63, (3): 864-882. doi:10.1083/jcb.63.3.864.