RRC ID 47646
著者 Quan X, Sato-Miyata Y, Tsuda M, Muramatsu K, Asano T, Takeo S, Aigaki T.
タイトル Deficiency of succinyl-CoA synthetase α subunit delays development, impairs locomotor activity and reduces survival under starvation in Drosophila.
ジャーナル Biochem Biophys Res Commun
Abstract Succinyl-CoA synthetase/ligase (SCS) is a mitochondrial enzyme that catalyzes the reversible process from succinyl-CoA to succinate and free coenzyme A in TCA cycle. SCS deficiencies are implicated in mitochondrial hepatoencephalomyopathy in humans. To investigate the impact of SCS deficiencies in Drosophila, we generated a null mutation in Scs alpha subunit (Scsα) using the CRISPR/Cas9 system, and characterized their phenotype. We found that the Drosophila SCS deficiency, designated ScsαKO, contained a high level of succinyl-CoA, a substrate for the enzyme, and altered levels of various metabolites in TCA cycle and glycolysis, indicating that the energy metabolism was impaired. Unlike SCSα deficiencies in humans, there was no reduction in lifespan, indicating that Scsα is not critical for viability in Drosophila. However, they showed developmental delays, locomotor activity defects, and reduced survival under starvation. We also found that glycogen breakdown occurred during development, suggesting that the mutant flies were unable to produce sufficient energy to promote normal growth. These results suggested that SCSα is essential for proper energy metabolism in Drosophila. The ScsαKO flies should be useful as a model to understand the physiological role of SCSα as well as the pathophysiology of SCSα deficiency.
巻・号 483(1)
ページ 566-571
公開日 2017-1-29
DOI 10.1016/j.bbrc.2016.12.105
PII S0006-291X(16)32165-9
PMID 28017724
MeSH Acyl Coenzyme A / deficiency* Acyl Coenzyme A / genetics Animals Animals, Genetically Modified Behavior, Animal Cell Survival Citric Acid Cycle Drosophila Proteins / deficiency* Drosophila Proteins / genetics Drosophila melanogaster / enzymology Drosophila melanogaster / genetics Drosophila melanogaster / physiology* Energy Metabolism* Food Deprivation* Glycogen / metabolism Glycolysis Locomotion* Male Mitochondria / metabolism Phenotype Starvation
IF 2.985
引用数 5
WOS 分野 BIOCHEMISTRY & MOLECULAR BIOLOGY BIOPHYSICS
リソース情報
ショウジョウバエ CAS-0002 TBX-0001