ND3, ND1 and 39kDa subunits are more exposed in the de-active form of bovine mitochondrial complex I

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
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 (S1) supercomplex, cysteine 39 is accessible for chemical modification in only the D-form. Using lysine-specific fluorescent labelling and a DIGE-like approach we further identified two new subunits involved in structural rearrangements during the A/D transition: ND1 (MT-ND1) and 39kDa (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.
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Metadaten
Author:Marion Babot, Paola Labarbuta, Amanda Birch, Sara Kee, Matthew Fuszard, Catherine H. Botting, Ilka Wittig, Heinrich Heide, Alexander Galkin
URN:urn:nbn:de:hebis:30:3-345543
DOI:http://dx.doi.org/10.1016/j.bbabio.2014.02.013
ISSN:1879-2650
ISSN:0005-2728
Pubmed Id:http://www.ncbi.nlm.nih.gov/pubmed?term=24560811
Parent Title (English):Biochimica et biophysica acta
Publisher:Elsevier
Place of publication:Amsterdam
Document Type:Article
Language:English
Date of Publication (online):2014/07/17
Date of first Publication:2014/02/21
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2014/07/17
Tag:A/D transition; Complex I; Conformational change; N-hydroxysuccinimide; NADH:ubiquinone oxidoreductase; Protein tyrosine modification
Volume:1837
Issue:6
Pagenumber:11
First Page:929
Last Page:939
Note:
Open Access funded by Medical Research Council. Under a Creative Commons license: http://creativecommons.org/licenses/by/3.0/
HeBIS PPN:452399521
Institutes:Medizin
Dewey Decimal Classification:610 Medizin und Gesundheit
Sammlungen:Universitätspublikationen
Licence (German):License LogoCreative Commons - Namensnennung 3.0

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