Quan Xiuming, Sato-Miyata Yukiko, Tsuda Manabu, Muramatsu Keigo, Asano Tsunaki, Takeo Satomi, Aigaki Toshiro
Department of Biological Sciences, Tokyo Metropolitan University, Japan.
Department of Liberal Arts and Human Development, Kanagawa University of Human Services, Japan.
Biochem Biophys Res Commun. 2017 Jan 29;483(1):566-571. doi: 10.1016/j.bbrc.2016.12.105. Epub 2016 Dec 23.
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 Scsα, 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 Scsα flies should be useful as a model to understand the physiological role of SCSα as well as the pathophysiology of SCSα deficiency.
琥珀酰辅酶A合成酶/连接酶（SCS）是一种线粒体酶，在三羧酸循环中催化从琥珀酰辅酶A到琥珀酸和游离辅酶A的可逆过程。SCS缺陷与人类线粒体性肝脑肌病有关。为了研究果蝇中SCS缺陷的影响，我们使用CRISPR/Cas9系统在Scsα亚基（Scsα）中产生了一个无效突变，并对其表型进行了表征。我们发现，果蝇SCS缺陷型（命名为Scsα）含有高水平的琥珀酰辅酶A（该酶的一种底物），并且三羧酸循环和糖酵解中各种代谢物的水平发生了改变，这表明能量代谢受到了损害。与人类的SCSα缺陷不同，果蝇的寿命没有缩短，这表明Scsα对果蝇的生存能力并不关键。然而，它们表现出发育延迟、运动活性缺陷以及饥饿条件下存活率降低。我们还发现，在发育过程中发生了糖原分解，这表明突变果蝇无法产生足够的能量来促进正常生长。这些结果表明，Scsα对果蝇正常的能量代谢至关重要。Scsα果蝇作为一种模型，对于理解Scsα的生理作用以及Scsα缺陷的病理生理学应该是有用的。
