title: Deficiency of succinyl-CoA synthetase α subunit delays development, impairs locomotor activity and reduces survival under starvation in Drosophila.
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 ScsαKOflies should be useful as a model to understand the physiological role of SCSα as well as the pathophysiology of SCSα deficiency.
authors.affiliation: Department of Biological Sciences, Tokyo Metropolitan University, Japan.
authors.forename: Xiuming
authors.initials: X
authors.lastname: Quan
authors.affiliation: Department of Biological Sciences, Tokyo Metropolitan University, Japan.
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Sato-Miyata
authors.affiliation: Department of Liberal Arts and Human Development, Kanagawa University of Human Services, Japan.
authors.forename: Manabu
authors.initials: M
authors.lastname: Tsuda
authors.affiliation: Department of Biological Sciences, Tokyo Metropolitan University, Japan.
authors.forename: Keigo
authors.initials: K
authors.lastname: Muramatsu
authors.affiliation: Department of Biological Sciences, Tokyo Metropolitan University, Japan.
authors.forename: Tsunaki
authors.initials: T
authors.lastname: Asano
authors.affiliation: Department of Biological Sciences, Tokyo Metropolitan University, Japan.
authors.forename: Satomi
authors.initials: S
authors.lastname: Takeo
authors.affiliation: Department of Biological Sciences, Tokyo Metropolitan University, Japan. Electronic address: aigaki-toshiro@tmu.ac.jp.
authors.forename: Toshiro
authors.initials: T
authors.lastname: Aigaki
mesh_terms: D000214:Acyl Coenzyme A / Q000172:deficiency* / Q000235:genetics; D000818:Animals; D030801:Animals, Genetically Modified; D001522:Behavior, Animal; D002470:Cell Survival; D002952:Citric Acid Cycle; D029721:Drosophila Proteins / Q000172:deficiency* / Q000235:genetics; D004331:Drosophila melanogaster / Q000201:enzymology / Q000235:genetics / Q000502:physiology*; D004734:Energy Metabolism; D005508:Food Deprivation; D006003:Glycogen / Q000378:metabolism; D006019:Glycolysis; D008124:Locomotion; D008297:Male; D008928:Mitochondria / Q000378:metabolism; D010641:Phenotype; D013217:Starvation
chemical_list: D000214:Acyl Coenzyme A; D029721:Drosophila Proteins; D006003:Glycogen; C012046:succinyl-coenzyme A
keywords: Developmental delay; Energy metabolism; Glycogen breakdown; SCS deficiency; Succinyl-CoA synthetase α subunit