title: Impaired energy metabolism in a Drosophila model of mitochondrial aconitase deficiency.
abstract: Aconitase catalyzes the conversion of citrate to isocitrate in the tricarboxylic acid (TCA) cycle, and its deficiency in humans is associated with an infantile neurodegenerative disorder affecting mainly the cerebellum and retina. Here we investigated the effect of gene knockout and knockdown of the mitochondrial aconitase Acon in Drosophila. Acon-knockout flies were homozygous lethal, indicating that Acon is essential for viability. RNA interference-generated Acon-knockdown flies exhibited a variety of phenotypes, such as reduced locomotor activity, a shortened lifespan, and increased cell death in the developing brain. Metabolomic analysis revealed that acetyl-CoA, citrate/isocitrate, and cis-aconitate were significantly increased, while most metabolites of glycolysis and the TCA cycle were reduced. Reduced triacylglyceride and increased acetyl-CoA suggested that lipids were used as an energy source because of the impaired glycolysis and TCA cycle. The Acon-knockdown model should facilitate further understanding of the pathophysiology of m-aconitase deficiency in humans.
authors: Department of Biological Sciences, Tokyo Metropolitan University, 1-1 Minami-osawa, Hachioji, Tokyo 192-0397, Japan.
authors: Zhang
authors: Z
authors: Cheng
authors: Manabu
authors: M
authors: Tsuda
authors: Yoshihito
authors: Y
authors: Kishita
authors: Yukiko
authors: Y
authors: Sato
authors: Toshiro
authors: T
authors: Aigaki
mesh_terms: D000105:Acetyl Coenzyme A / Q000378:metabolism; D000154:Aconitate Hydratase / Q000172:deficiency* / Q000235:genetics; D000818:Animals; D001483:Base Sequence; D016923:Cell Death; D002952:Citric Acid Cycle; D017931:DNA Primers / Q000235:genetics; D029721:Drosophila Proteins / Q000172:deficiency* / Q000235:genetics; D004331:Drosophila melanogaster / Q000235:genetics / Q000378:metabolism*; D004734:Energy Metabolism; D005260:Female; D055785:Gene Knockdown Techniques; D055786:Gene Knockout Techniques; D017344:Genes, Insect; D006019:Glycolysis; D050356:Lipid Metabolism; D008136:Longevity; D055442:Metabolome; D008928:Mitochondria / Q000378:metabolism; D008954:Models, Biological; D009043:Motor Activity; D009474:Neurons / Q000166:cytology; D010641:Phenotype; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014280:Triglycerides / Q000378:metabolism
chemical_list: D017931:DNA Primers; D029721:Drosophila Proteins; D012333:RNA, Messenger; D014280:Triglycerides; D000105:Acetyl Coenzyme A; D000154:Aconitate Hydratase