Human mitochondrial COX1 assembly into cytochrome c oxidase at a glance
Human mitochondrial COX1 assembly into cytochrome c oxidase at a glance
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DOI：
10.1242/jcs.161729
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发表时间：
2015-03-01
影响因子：
4
通讯作者：
Rehling, Peter
中科院分区：
文献类型：
--
作者：
Dennerlein, Sven;Rehling, Peter
线粒体以由F1Fo ATP合酶产生的ATP形式提供细胞能量的主要部分，其使用由线粒体呼吸链（MRC）产生的电化学梯度。在人类线粒体中，MRC由四种多亚基酶复合物组成，其中细胞色素c氧化酶（考克斯，也称为复合物IV）作为末端酶。考克斯由14个核或线粒体来源的结构亚基组成。因此，线粒体面临着组织和控制考克斯与由不同翻译机器合成并通过替代运输途径到达内膜的亚基组装的困境。近年来，越来越多的考克斯组装因子被发现。有趣的是，这些因子中的几种突变与导致考克斯缺乏的人类疾病相关。最近，研究提供了机械的见解组装中间体，进口过程和考克斯亚基在线粒体中的合成之间的串扰，从而连接概念上分离的功能。这篇细胞科学一瞥文章和随附的海报将集中在考克斯组装和讨论在该领域的最新发现，已知因素的分子功能，以及新的球员和控制机制。此外，这些发现将在人类COX相关疾病的背景下进行讨论。
Mitochondria provide the main portion of cellular energy in form of ATP produced by the F1Fo ATP synthase, which uses the electrochemical gradient, generated by the mitochondrial respiratory chain (MRC). In human mitochondria, the MRC is composed of four multisubunit enzyme complexes, with the cytochrome c oxidase (COX, also known as complex IV) as the terminal enzyme. COX comprises 14 structural subunits, of nuclear or mitochondrial origin. Hence, mitochondria are faced with the predicament of organizing and controlling COX assembly with subunits that are synthesized by different translation machineries and that reach the inner membrane by alternative transport routes. An increasing number of COX assembly factors have been identified in recent years. Interestingly, mutations in several of these factors have been associated with human disorders leading to COX deficiency. Recently, studies have provided mechanistic insights into crosstalk between assembly intermediates, import processes and the synthesis of COX subunits in mitochondria, thus linking conceptually separated functions. This Cell Science at a Glance article and the accompanying poster will focus on COX assembly and discuss recent discoveries in the field, the molecular functions of known factors, as well as new players and control mechanisms. Furthermore, these findings will be discussed in the context of human COX-related disorders.