Coenzyme Q biosynthesis in health and disease
Coenzyme Q biosynthesis in health and disease
复制标题
DOI：
10.1016/j.bbabio.2016.03.036
复制
发表时间：
2016-08-01
影响因子：
4.3
通讯作者：
Salviati, Leonardo
中科院分区：
文献类型：
--
作者：
Acosta, Manuel Jesus;Fonseca, Luis Vazquez;Salviati, Leonardo
辅酶Q（CoQ或泛醌）是一种显著的脂质，其在线粒体中作为呼吸链的复合物I和II与复合物III之间的电子穿梭发挥重要作用。它也是其他辅酶A酶的辅因子、渗透性转换孔的调节剂和必需的抗氧化剂。辅酶Q在线粒体中由一组至少12种蛋白质合成，形成多蛋白复合物。这个复合体的确切组成尚不清楚。大多数参与辅酶Q生物合成的基因（COQ基因）已在酵母中进行了研究，并具有哺乳动物直向同源物。其中一些编码参与辅酶Q醌环修饰的酶，但对于其他酶，其确切功能尚不清楚。两个基因似乎具有调节作用：COQ8（及其人类对应物ADCK 3和ADCK 4）编码一种推定的激酶，而PTC 7编码激活Coq 7所需的磷酸酶。人类辅酶Q基因的突变导致原发性辅酶Q（10）缺乏症，这是一种从出生到70岁发病的临床异质性线粒体疾病，临床表现包括致命的多系统疾病，CoQ（10）缺乏症的发病机制涉及ATP产生不足和ROS形成过多，但可能涉及CoQ（10）功能的其他方面。CoQ（10）缺乏症在线粒体疾病中是独特的，因为有效的治疗是可用的。许多患者对口服CoQw补充剂有反应。然而，由于该化合物的生物利用度低，治疗仍然存在问题，目前正在研究新的药理学方法。这篇文章是题为“EBEC 2016：第19届欧洲生物能量学会议，加尔达湖滨，意大利，2016年7月2日至6日”的特刊的一部分，由Paolo Bernardi教授编辑。(C)2016由Elsevier B.V.出版
Coenzyme Q(CoQ or ubiquinone) is a remarkable lipid that plays an essential role in mitochondria as an electron shuttle between complexes I and II of the respiratory chain, and complex III. It is also a cofactor of other dehydrogenases, a modulator of the permeability transition pore and an essential antioxidant.CoQ is synthesized in mitochondria by a set of at least 12 proteins that form a multiprotein complex. The exact composition of this complex is still unclear. Most of the genes involved in CoQ biosynthesis (COQ genes) have been studied in yeast and have mammalian orthologues. Some of them encode enzymes involved in the modification of the quinone ring of CoQ but for others the precise function is unknown. Two genes appear to have a regulatory role: COQ8 (and its human counterparts ADCK3 and ADCK4) encodes a putative kinase, while PTC7 encodes a phosphatase required for the activation of Coq7.Mutations in human COQgenes cause primary CoQ(10) deficiency, a clinically heterogeneous mitochondrial disorder with onset from birth to the seventh decade, and with clinical manifestation ranging from fatal multisystem disorders, to isolated encephalopathy or nephropathy.The pathogenesis of CoQ(10) deficiency involves deficient ATP production and excessive ROS formation, but possibly other aspects of CoQ(10) function are implicated.CoQ(10) deficiency is unique among mitochondrial disorders since an effective treatment is available. Many patients respond to oral CoQw supplementation. Nevertheless, treatment is still problematic because of the low bioavailability of the compound, and novel pharmacological approaches are currently being investigated. This article is part of a Special Issue entitled 'EBEC 2016: 19th European Bioenergetics Conference, Riva del Garda, Italy, July 2-6, 2016', edited by Prof. Paolo Bernardi. (C) 2016 Published by Elsevier B.V.