Mutations at the flavin binding site of ETF:QO yield a MADD-like severe phenotype in Drosophila

Biochimica Et Biophysica Acta
Ema AlvesCláudio M Gomes

Abstract

Following a screening on EMS-induced Drosophila mutants defective for formation and morphogenesis of epithelial cells, we have identified three lethal mutants defective for the production of embryonic cuticle. The mutants are allelic to the CG12140 gene, the fly homologue of electron transfer flavoprotein:ubiquinone oxidoreductase (ETF:QO). In humans, inherited defects in this inner membrane protein account for multiple acyl-CoA dehydrogenase deficiency (MADD), a metabolic disease of β-oxidation, with a broad range of clinical phenotypes, varying from embryonic lethal to mild forms. The three mutant alleles carried distinct missense mutations in ETF:QO (G65E, A68V and S104F) and maternal mutant embryos for ETF:QO showed lethal morphogenetic defects and a significant induction of apoptosis following germ-band elongation. This phenotype is accompanied by an embryonic accumulation of short- and medium-chain acylcarnitines (C4, C8 and C12) as well as long-chain acylcarnitines (C14 and C16:1), whose elevation is also found in severe MADD forms in humans under intense metabolic decompensation. In agreement the ETF:QO activity in the mutant embryos is markedly decreased in relation to wild type activity. Amino acid sequence analysis a...Continue Reading

References

Aug 1, 1978·Analytical Biochemistry·C Watters
Mar 1, 1990·Journal of Molecular Graphics·G Vriend
Mar 1, 1989·American Journal of Medical Genetics·G N WilsonS I Goodman
Aug 15, 1993·Proceedings of the National Academy of Sciences of the United States of America·J J KimR Paschke
Dec 10, 1996·Proceedings of the National Academy of Sciences of the United States of America·D L RobertsJ J Kim
Mar 29, 2000·Critical Reviews in Clinical Laboratory Sciences·M J BennettA W Strauss
May 18, 2005·Molecular Genetics and Metabolism·Nadia A OeyRonald J A Wanders
May 26, 2005·Protein Expression and Purification·F William Studier
Aug 27, 2005·PLoS Genetics·Ravi J TolwaniPhilip A Wood
Jan 26, 2006·Proceedings of the National Academy of Sciences of the United States of America·Philippos MourikisSpyros Artavanis-Tsakonas
Apr 8, 2006·Journal of Inherited Metabolic Disease·Nadia A OeyFrits A Wijburg
Oct 20, 2006·Proceedings of the National Academy of Sciences of the United States of America·Jian ZhangJung-Ja P Kim
Aug 12, 2008·Mini Reviews in Medicinal Chemistry·Paula Leandro, Cláudio M Gomes
Sep 20, 2008·Developmental Biology·Ana Pimenta-MarquesRui Gonçalo Martinho
Jul 30, 2009·Journal of Molecular Evolution·Zuzana SwigonováJerry Vockley
Jan 13, 2010·PloS One·Daniel J M Fernández-AyalaHoward T Jacobs
Aug 24, 2010·Biochemical and Biophysical Research Communications·Helen SkillingEric S Goetzman
Dec 29, 2010·Journal of Proteome Research·Charlotte Welinder, Lars Ekblad
Oct 5, 2011·Biochimica Et Biophysica Acta·Tânia G LucasCláudio M Gomes
May 17, 2012·Free Radical Biology & Medicine·João V Rodrigues, Cláudio M Gomes

❮ Previous
Next ❯

Related Concepts

Related Feeds

Auditory Perception

Auditory perception is the ability to receive and interpret information attained by the ears. Here is the latest research on factors and underlying mechanisms that influence auditory perception.

Birth Defects

Birth defects encompass structural and functional alterations that occur during embryonic or fetal development and are present since birth. The cause may be genetic, environmental or unknown and can result in physical and/or mental impairment. Here is the latest research on birth defects.