Characterisation of the active/de-active transition of mitochondrial complex I.
Characterisation of the active/de-active transition of mitochondrial complex I.
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DOI：
10.1016/j.bbabio.2014.02.018
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发表时间：
2014-07
影响因子：
4.3
通讯作者：
Galkin, Alexander
中科院分区：
文献类型：
--
作者：
Babot, Marion;Birch, Amanda;Labarbuta, Paola;Galkin, Alexander
关键词：
线粒体复合物I催化需氧细胞线粒体基质中NADH的氧化。这种线粒体酶的调节还不完全清楚。来自某些生物体的复合物I的一个有趣的特征是能够采用两种不同的状态：所谓的催化活性（A）和失活的休眠状态（D）。当呼吸链的活性受到限制时（即，在不存在氧气的情况下），A型可以原位失活。该酶的A/D转换背后的机制和驱动力目前尚不清楚，但几个亚基最有可能参与构象重排：辅助亚基39 kDa（NDUFA 9）和蛋白质编码的亚基ND 3和ND 1。这三个亚基位于醌结合位点的区域。A/D转换可能代表了线粒体呼吸链对缺氧的快速反应的内在机制。缺氧时D-型积累的生理作用最可能是保护线粒体免受再氧合后呼吸快速爆发引起的ROS生成。失活率在不同组织中变化，并且可以通过温度、游离脂肪酸和二价阳离子的存在、基质中的NAD+/NADH比率、一氧化氮的存在和氧可用性来调节。ND 3亚基的半胱氨酸-39以D-形式暴露，容易被亚硝基硫醇、ROS和RNS进行共价修饰。D-型在原位可以与线粒体中的天然效应物或药理学试剂反应。因此，调节复合物I的再激活速率可能是改善缺血/再灌注损伤的一种途径。本文是题为：第18届欧洲生物能源会议特刊的一部分。客座编辑：Manuela佩雷拉和Miguel特谢拉。讨论了络合物I A/D转变的可能机制。暴露在D-型中的-SH基团易于共价修饰。提出了A/D转变在组织对缺血反应中的作用。
Oxidation of NADH in the mitochondrial matrix of aerobic cells is catalysed by mitochondrial complex I. The regulation of this mitochondrial enzyme is not completely understood. An interesting characteristic of complex I from some organisms is the ability to adopt two distinct states: the so-called catalytically active (A) and the de-active, dormant state (D). The A-form in situ can undergo de-activation when the activity of the respiratory chain is limited (i.e. in the absence of oxygen). The mechanisms and driving force behind the A/D transition of the enzyme are currently unknown, but several subunits are most likely involved in the conformational rearrangements: the accessory subunit 39 kDa (NDUFA9) and the mitochondrially encoded subunits, ND3 and ND1. These three subunits are located in the region of the quinone binding site. The A/D transition could represent an intrinsic mechanism which provides a fast response of the mitochondrial respiratory chain to oxygen deprivation. The physiological role of the accumulation of the D-form in anoxia is most probably to protect mitochondria from ROS generation due to the rapid burst of respiration following reoxygenation. The de-activation rate varies in different tissues and can be modulated by the temperature, the presence of free fatty acids and divalent cations, the NAD+/NADH ratio in the matrix, the presence of nitric oxide and oxygen availability. Cysteine-39 of the ND3 subunit, exposed in the D-form, is susceptible to covalent modification by nitrosothiols, ROS and RNS. The D-form in situ could react with natural effectors in mitochondria or with pharmacological agents. Therefore the modulation of the re-activation rate of complex I could be a way to ameliorate the ischaemia/reperfusion damage. This article is part of a Special Issue entitled: 18th European Bioenergetic Conference. Guest Editors: Manuela Pereira and Miguel Teixeira. The potential mechanism of complex I A/D transition is discussed. An —SH group exposed in the D-form is susceptible to covalent modification. The role of A/D transition in tissue response to ischaemia is proposed.
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影响因子：
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作者：
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DOI：
10.1124/jpet.105.091702
发表时间：
2006-01-01
影响因子：
3.5
作者：
Chen, Q;Hoppel, CL;Lesnefsky, EJ
通讯作者：
Lesnefsky, EJ