Zinc accumulation in heterozygous mutants of fumble, the pantothenate kinase homologue of Drosophila.
Coenzyme A (CoA) functions in the intracellular trafficking of acetyl groups. In humans, mutations in the pantothenate kinase-2 gene, which encodes a key enzyme in CoA biosynthesis, are associated with neurodegeneration and premature death. Diagnosis is based on iron accumulation in the globus pallidus observed by magnetic resonance imaging. We investigated the elemental composition of the fumble mutant, a model of the human disease. Surprisingly, flies carrying a fumble loss-of-function allele had a three-fold increase in total zinc levels per dry weight when compared to control strains, but no change in total iron, copper or manganese levels. Accordingly, zinc supplementation had an adverse impact on the development of fumble mutant larvae, but zinc chelation failed to protect.
Gutiérrez
Lucia
L
School of Biological and Chemical Sciences, Queen Mary University of London, London, UK.
Sabaratnam
Narmatha
N
Aktar
Rubina
R
Bettedi
Lucia
L
Mandilaras
Konstantinos
K
Missirlis
Fanis
F
D000818:Animals; D004330:Drosophila / Q000235:genetics / Q000378:metabolism*; D005293:Ferritins / Q000378:metabolism; D006579:Heterozygote; D006801:Humans; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015032:Zinc / Q000378:metabolism*
D005293:Ferritins; D017853:Phosphotransferases (Alcohol Group Acceptor); C023088:pantothenate kinase; D015032:Zinc