Succinyl-CoA Synthetase Dysfunction as a Mechanism of Mitochondrial Encephalomyopathy: More than Just an Oxidative Energy Deficit.
Succinyl-CoA Synthetase Dysfunction as a Mechanism of Mitochondrial Encephalomyopathy: More than Just an Oxidative Energy Deficit.
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DOI：
10.3390/ijms241310725
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发表时间：
2023-06-27
影响因子：
5.6
通讯作者：
中科院分区：
文献类型：
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作者：
三羧酸（TCA）循环酶琥珀酰辅酶a合成酶（SCS）亚基的双等位致病变异与人类线粒体脑肌病有关。SCS在TCA循环中催化琥珀酰辅酶a到琥珀酸盐的相互转化，并与底物水平的ADP或GDP磷酸化相结合。scs缺陷性脑肌病通常出现在婴儿期和幼儿期，许多患者在儿童期就死于这种疾病。常见症状包括脑MRI异常、基底节区病变和脑萎缩、严重张力低下、肌张力障碍、进行性精神运动减退和生长缺陷。虽然在21世纪初，SCS亚基首次被确定为进行性代谢性脑肌病的致病基因，但最近的研究开始揭示这种代谢性疾病的病理机制。本文回顾了目前对TCA循环内外SCS功能的理解，因为它涉及SCS相关线粒体脑肌病的复杂和多因素机制。
Biallelic pathogenic variants in subunits of succinyl-CoA synthetase (SCS), a tricarboxylic acid (TCA) cycle enzyme, are associated with mitochondrial encephalomyopathy in humans. SCS catalyzes the interconversion of succinyl-CoA to succinate, coupled to substrate-level phosphorylation of either ADP or GDP, within the TCA cycle. SCS-deficient encephalomyopathy typically presents in infancy and early childhood, with many patients succumbing to the disease during childhood. Common symptoms include abnormal brain MRI, basal ganglia lesions and cerebral atrophy, severe hypotonia, dystonia, progressive psychomotor regression, and growth deficits. Although subunits of SCS were first identified as causal genes for progressive metabolic encephalomyopathy in the early 2000s, recent investigations are now beginning to unravel the pathomechanisms underlying this metabolic disorder. This article reviews the current understanding of SCS function within and outside the TCA cycle as it relates to the complex and multifactorial mechanisms underlying SCS-related mitochondrial encephalomyopathy.
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影响因子：
5.6
作者：
Fasullo M;Endres L
通讯作者：
Endres L
影响因子：
4.2
作者：
Carrozzo, Rosalba;Verrigni, Daniela;Ostergaard, Elsebet
通讯作者：
Ostergaard, Elsebet
影响因子：
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作者：
通讯作者：
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影响因子：
14.5
作者：
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通讯作者：
Wevers, Ron A.
影响因子：
1.9
作者：
Garone, Caterina;Gurgel-Giannetti, Juliana;Hirano, Michio
通讯作者：
Hirano, Michio