期刊
BIOCHIMICA ET BIOPHYSICA ACTA-BIOENERGETICS
卷 1837, 期 6, 页码 929-939出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.bbabio.2014.02.013
关键词
Complex I; NADH:ubiquinone oxidoreductase; A/D transition; Conformational change; Protein tyrosine modification; N-hydroxysuccinimide
资金
- MRC [G1100051]
- Cluster of Excellence Macromolecular Complexes at the Goethe University Frankfurt [EXC 115]
- Deutsche Forschungsgemeinschaft Sonderforschungsbereich 815 project Z1-Redox-Proteomics
- Bundesministerium fur Bildung und Forschung Grant BMBF mitoNET-Deutsches Netzwerk fur mitochondriale Erkrankungen [01GM1113B]
- MRC [G1100051] Funding Source: UKRI
- Medical Research Council [G1100051] Funding Source: researchfish
An intriguing feature of mitochondrial complex I from several species is the so-called A/D transition, whereby the idle enzyme spontaneously converts from the active (A) form to the de-active (D) form. The A/D transition plays an important role in tissue response to the lack of oxygen and hypoxic deactivation of the enzyme is one of the key regulatory events that occur in mitochondria during ischaemia. We demonstrate for the first time that the A/D conformational change of complex I does not affect the macromolecular organisation of supercomplexes in vitro as revealed by two types of native electrophoresis. Cysteine 39 of the mitochondrially-encoded ND3 subunit is known to become exposed upon de-activation. Here we show that even if complex I is a constituent of the I + III2 + IV (S-1) supercomplex, cysteine 39 is accessible for chemical modification in only the D-form. Using lysine-specific fluorescent labelling and a DICE-like approach we further identified two new subunits involved in structural rearrangements during the A/D transition: ND1 (MT-ND1) and 39 kDa (NDUFA9). These results clearly show that structural rearrangements during de-activation of complex I include several subunits located at the junction between hydrophilic and hydrophobic domains, in the region of the quinone binding site. De-activation of mitochondrial complex I results in concerted structural rearrangement of membrane subunits which leads to the disruption of the sealed quinone chamber required for catalytic turnover. Crown Copyright (C) 2014 Published by Elsevier B.V. All rights reserved.
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