Regulation of the CoA Biosynthetic Complex Assembly in Mammalian Cells.
Regulation of the CoA Biosynthetic Complex Assembly in Mammalian Cells.
复制标题
哺乳动物细胞中CoA生物合成复合物组装的调节。
DOI：
10.3390/ijms22031131
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发表时间：
2021-01-24
影响因子：
5.6
通讯作者：
Gout I
中科院分区：
文献类型：
--
作者：
Baković J;López Martínez D;Nikolaou S;Yu BYK;Tossounian MA;Tsuchiya Y;Thrasivoulou C;Filonenko V;Gout I
辅酶A（CoA）是存在于所有活细胞中的必需辅因子。在生理条件下，CoA主要功能是产生代谢活性的CoA硫酯，其对于细胞代谢、基因表达的调节和神经递质的生物合成是不可缺少的。当细胞暴露于氧化或代谢应激时，CoA作为一种重要的细胞抗氧化剂，保护蛋白质巯基免受过度氧化，并且该功能由蛋白质CoAlation介导。辅酶A及其衍生物严格维持在由营养素、激素、代谢物和细胞应激控制的水平。它们的生物合成和体内平衡的失调具有有害的后果，并且已经在一系列病理状况中注意到，包括癌症、糖尿病、Reye综合征、心脏肥大和神经变性。辅酶A生物合成的生物化学涉及五个酶促步骤，已被广泛研究。然而，CoA生物合成复合物的存在及其在哺乳动物细胞中的调节模式是未知的。在这项研究中，我们报告了所有五种驱动CoA生物合成的酶在HEK 293/Pank 1 β和A549细胞中的组装，使用原位邻近连接试验。此外，我们发现，辅酶A生物合成酶的协会强烈上调血清饥饿和氧化应激，而胰岛素和生长因子信号下调其组装。
Coenzyme A (CoA) is an essential cofactor present in all living cells. Under physiological conditions, CoA mainly functions to generate metabolically active CoA thioesters, which are indispensable for cellular metabolism, the regulation of gene expression, and the biosynthesis of neurotransmitters. When cells are exposed to oxidative or metabolic stress, CoA acts as an important cellular antioxidant that protects protein thiols from overoxidation, and this function is mediated by protein CoAlation. CoA and its derivatives are strictly maintained at levels controlled by nutrients, hormones, metabolites, and cellular stresses. Dysregulation of their biosynthesis and homeostasis has deleterious consequences and has been noted in a range of pathological conditions, including cancer, diabetes, Reye’s syndrome, cardiac hypertrophy, and neurodegeneration. The biochemistry of CoA biosynthesis, which involves five enzymatic steps, has been extensively studied. However, the existence of a CoA biosynthetic complex and the mode of its regulation in mammalian cells are unknown. In this study, we report the assembly of all five enzymes that drive CoA biosynthesis, in HEK293/Pank1β and A549 cells, using the in situ proximity ligation assay. Furthermore, we show that the association of CoA biosynthetic enzymes is strongly upregulated in response to serum starvation and oxidative stress, whereas insulin and growth factor signaling downregulate their assembly.
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影响因子：
4.8
作者：
Fiermonte, Giuseppe;Paradies, Eleonora;Palmieri, Ferdinando
通讯作者：
Palmieri, Ferdinando
影响因子：
14.8
作者：
Ruiz, Amparo;Gonzalez, Asier;Arino, Joaquin
通讯作者：
Arino, Joaquin
DOI：
10.1126/science.1230593
发表时间：
2013-03-15
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Rhee HW;Zou P;Udeshi ND;Martell JD;Mootha VK;Carr SA;Ting AY
通讯作者：
Ting AY
影响因子：
8.8
作者：
McAllister, R A;Fixter, L M;Campbell, E H
通讯作者：
Campbell, E H
影响因子：
4.8
作者：
Calder, RB;Williams, RSB;Jackowski, S
通讯作者：
Jackowski, S