| RRC ID |
22005
|
| 著者 |
Cheng Z, Tsuda M, Kishita Y, Sato Y, Aigaki T.
|
| タイトル |
Impaired energy metabolism in a Drosophila model of mitochondrial aconitase deficiency.
|
| ジャーナル |
Biochem Biophys Res Commun
|
| 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.
|
| 巻・号 |
433(1)
|
| ページ |
145-50
|
| 公開日 |
2013-3-29
|
| DOI |
10.1016/j.bbrc.2013.02.040
|
| PII |
S0006-291X(13)00300-8
|
| PMID |
23438437
|
| MeSH |
Acetyl Coenzyme A / metabolism
Aconitate Hydratase / deficiency*
Aconitate Hydratase / genetics
Animals
Base Sequence
Cell Death
Citric Acid Cycle
DNA Primers / genetics
Drosophila Proteins / deficiency*
Drosophila Proteins / genetics
Drosophila melanogaster / genetics
Drosophila melanogaster / metabolism*
Energy Metabolism
Female
Gene Knockdown Techniques
Gene Knockout Techniques
Genes, Insect
Glycolysis
Lipid Metabolism
Longevity
Metabolome
Mitochondria / metabolism
Models, Biological
Motor Activity
Neurons / cytology
Phenotype
RNA, Messenger / genetics
RNA, Messenger / metabolism
Triglycerides / metabolism
|
| IF |
2.985
|
| 引用数 |
16
|
|
WOS 分野
|
BIOPHYSICS
BIOCHEMISTRY & MOLECULAR BIOLOGY
|
| リソース情報 |
| ショウジョウバエ |
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