ND3 Cys39 in complex I is exposed during mitochondrial respiration.
ND3 Cys39 in complex I is exposed during mitochondrial respiration.
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DOI：
10.1016/j.chembiol.2021.10.010
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发表时间：
2022-04-21
影响因子：
8.6
通讯作者：
Murphy, Michael P.
中科院分区：
文献类型：
--
作者：
Burger, Nils;James, Andrew M.;Mulvey, John F.;Hoogewijs, Kurt;Ding, Shujing;Fearnley, Ian M.;Loureiro-Lopez, Marta;Norman, Abigail A., I;Arndt, Sabine;Mottahedin, Amin;Sauchanka, Olga;Hartley, Richard C.;Krieg, Thomas;Murphy, Michael P.
哺乳动物复合物I可以采用催化活性（A-）或失活（D-）状态。这两种定义状态之间可逆转变的定义特征被认为是ND 3亚基Cys 39残基在D-状态中的暴露和其在A-状态中的闭塞。由于催化A/D转换在健康和疾病中很重要，我们开始通过使用同位素标记和质谱法测量Cys 39暴露来量化它，同时测量复合物I NADH/CoQ氧化还原酶活性。令我们惊讶的是，我们发现在NADH/CoQ氧化还原酶活性期间显著的Cys 39暴露。此外，如果Cys 39烷基化发生在复合物I连接的呼吸过程中，则该活性不受影响。相比之下，催化失活的复合物I的烷基化不可逆地阻断了NADH/辅酶Q氧化还原酶活性由NADH的再活化。因此，ND 3的Cys 39在线粒体呼吸过程中暴露于复合物I中，对于我们理解A/D转换和复合物I的机制具有重要意义。复合物I中的ND 3-Cys 39在活性线粒体呼吸期间暴露活性复合物I中暴露的Cys 39的修饰不损害呼吸失活复合物I中暴露的Cys 39的修饰防止再活化复合物I活性和Cys 39暴露不直接相关复合物I的神秘活性/失活转变与关键ND 3-Cys 39残基的暴露状态相关，作为关键指标。Burger等人显示Cys 39在复合物I连接的呼吸过程中暴露，对于理解活性/失活过渡和复合物I功能具有重要意义。
Mammalian complex I can adopt catalytically active (A-) or deactive (D-) states. A defining feature of the reversible transition between these two defined states is thought to be exposure of the ND3 subunit Cys39 residue in the D-state and its occlusion in the A-state. As the catalytic A/D transition is important in health and disease, we set out to quantify it by measuring Cys39 exposure using isotopic labeling and mass spectrometry, in parallel with complex I NADH/CoQ oxidoreductase activity. To our surprise, we found significant Cys39 exposure during NADH/CoQ oxidoreductase activity. Furthermore, this activity was unaffected if Cys39 alkylation occurred during complex I-linked respiration. In contrast, alkylation of catalytically inactive complex I irreversibly blocked the reactivation of NADH/CoQ oxidoreductase activity by NADH. Thus, Cys39 of ND3 is exposed in complex I during mitochondrial respiration, with significant implications for our understanding of the A/D transition and the mechanism of complex I. ND3-Cys39 in complex I is exposed during active mitochondrial respiration Modification of exposed Cys39 in active complex I does not impair respiration Modification of exposed Cys39 in deactive complex I prevents reactivation Complex I activity and Cys39 exposure are not linked directly The enigmatic active/deactive transition of complex I is linked to the exposure state of the critical ND3-Cys39 residue, functioning as critical indicator. Burger et al. show that Cys39 is exposed during complex I-linked respiration with important implications for the understanding of the active/deactive transition and complex I function.
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影响因子：
64.8
作者：
Fiedorczuk, Karol;Letts, James A.;Degliesposti, Gianluca;Kaszuba, Karol;Skehel, Mark;Sazanov, Leonid A.
通讯作者：
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影响因子：
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作者：
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通讯作者：
Galkin, Alexander
影响因子：
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作者：
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