Redox-Mediated Regulation of Mitochondrial Biogenesis, Dynamics, and Respiratory Chain Assembly in Yeast and Human Cells.
Redox-Mediated Regulation of Mitochondrial Biogenesis, Dynamics, and Respiratory Chain Assembly in Yeast and Human Cells.
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DOI：
10.3389/fcell.2021.720656
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发表时间：
2021
影响因子：
5.5
通讯作者：
Tokatlidis K
中科院分区：
文献类型：
--
作者：
Geldon S;Fernández-Vizarra E;Tokatlidis K
线粒体是双层细胞器，包含它们自己的基因组，线粒体DNA(MtDNA)，这让人想起它的内生共生起源。线粒体通过位于线粒体内膜的电子氧化磷酸化系统(OXPHOS)和三磷酸腺苷合成酶(复合体V)负责细胞的呼吸作用。尽管线粒体DNA编码重要的OXPHOS组分，但绝大多数结构亚基和附加的生物发生因子(70多个蛋白质)是在细胞核中编码并在细胞质中翻译的。为了将这些蛋白质和线粒体蛋白质组的其余部分结合在一起，线粒体进化出了各种复杂的输入机制，这些机制专门针对由两层膜定义的不同隔室的蛋白质。膜间隙(IMS)含有大量的富含半胱氨酸的蛋白质，主要通过MIA40氧化折叠系统输入，依赖于关键半胱氨酸残基的还原和氧化。其中一些蛋白质是ETC复合体正确成熟和功能所必需的结构成分或组装因子。有趣的是，这些蛋白质中的许多都参与了复合体IV的活性氧化还原中心的金属化，以及线粒体的末端氧化酶等。由于线粒体在氧还原中的作用，它们是内膜两侧，即基质和IMS中的活性氧物种(ROS)的主要生成者。ROS的产生很重要，因为它们是信号分子，但过量的产生是有害的，因为不必要的氧化反应会影响线粒体中不同类型的生物分子的功能。因此，IMS中氧化还原平衡的维持对线粒体的功能至关重要。在这篇综述中，我们将讨论氧化还原调节在维持IMS动态平衡中的作用，以及线粒体ROS的产生如何可能是ETC生物发生的关键调控因素，特别是对复合体IV。
Mitochondria are double-membrane organelles that contain their own genome, the mitochondrial DNA (mtDNA), and reminiscent of its endosymbiotic origin. Mitochondria are responsible for cellular respiration via the function of the electron oxidative phosphorylation system (OXPHOS), located in the mitochondrial inner membrane and composed of the four electron transport chain (ETC) enzymes (complexes I-IV), and the ATP synthase (complex V). Even though the mtDNA encodes essential OXPHOS components, the large majority of the structural subunits and additional biogenetical factors (more than seventy proteins) are encoded in the nucleus and translated in the cytoplasm. To incorporate these proteins and the rest of the mitochondrial proteome, mitochondria have evolved varied, and sophisticated import machineries that specifically target proteins to the different compartments defined by the two membranes. The intermembrane space (IMS) contains a high number of cysteine-rich proteins, which are mostly imported via the MIA40 oxidative folding system, dependent on the reduction, and oxidation of key Cys residues. Several of these proteins are structural components or assembly factors necessary for the correct maturation and function of the ETC complexes. Interestingly, many of these proteins are involved in the metalation of the active redox centers of complex IV, the terminal oxidase of the mitochondrial ETC. Due to their function in oxygen reduction, mitochondria are the main generators of reactive oxygen species (ROS), on both sides of the inner membrane, i.e., in the matrix and the IMS. ROS generation is important due to their role as signaling molecules, but an excessive production is detrimental due to unwanted oxidation reactions that impact on the function of different types of biomolecules contained in mitochondria. Therefore, the maintenance of the redox balance in the IMS is essential for mitochondrial function. In this review, we will discuss the role that redox regulation plays in the maintenance of IMS homeostasis as well as how mitochondrial ROS generation may be a key regulatory factor for ETC biogenesis, especially for complex IV.
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DOI：
10.1083/jcb.201708044
发表时间：
2018-04-02
期刊：
The Journal of cell biology
影响因子：
--
作者：
Backes S;Hess S;Boos F;Woellhaf MW;Gödel S;Jung M;Mühlhaus T;Herrmann JM
通讯作者：
Herrmann JM
影响因子：
5.6
作者：
Banci, Lucia;Bertini, Ivano;Tokatlidis, Kostas
通讯作者：
Tokatlidis, Kostas
影响因子：
9.8
作者：
Alston, Charlotte L.;Veling, Mike T.;Taylor, Robert W.
通讯作者：
Taylor, Robert W.
影响因子：
15
作者：
Banci, Lucia;Bertini, Ivano;Tokatlidis, Kostas
通讯作者：
Tokatlidis, Kostas
影响因子：
7.8
作者：
Becker, Thomas;Wenz, Lena-Sophie;Pfanner, Nikolaus
通讯作者：
Pfanner, Nikolaus