TY  - JOUR
A1  - Dröse, Stefan
A1  - Krack, Stephanie
A1  - Sokolova, Lucie
A1  - Zwicker, Klaus
A1  - Barth, Hans-Dieter
A1  - Morgner, Nina
A1  - Heide, Heinrich
A1  - Steger, Mirco
A1  - Nübel, Esther
A1  - Zickermann, Volker
A1  - Kerscher, Stefan
A1  - Brutschy, Bernd
A1  - Radermacher, Michael
A1  - Brandt, Ulrich
T1  - Functional dissection of the proton pumping modules of mitochondrial complex I
T2  - PLoS biology
N2  - Mitochondrial complex I, the largest and most complicated proton pump of the respiratory chain, links the electron transfer from NADH to ubiquinone to the pumping of four protons from the matrix into the intermembrane space. In humans, defects in complex I are involved in a wide range of degenerative disorders. Recent progress in the X-ray structural analysis of prokaryotic and eukaryotic complex I confirmed that the redox reactions are confined entirely to the hydrophilic peripheral arm of the L-shaped molecule and take place at a remarkable distance from the membrane domain. While this clearly implies that the proton pumping within the membrane arm of complex I is driven indirectly via long-range conformational coupling, the molecular mechanism and the number, identity, and localization of the pump-sites remains unclear. Here, we report that upon deletion of the gene for a small accessory subunit of the Yarrowia complex I, a stable subcomplex (nb8m delta) is formed that lacks the distal part of the membrane domain as revealed by single particle analysis. The analysis of the subunit composition of holo and subcomplex by three complementary proteomic approaches revealed that two (ND4 and ND5) of the three subunits with homology to bacterial Mrp-type Na+/H+ antiporters that have been discussed as prime candidates for harbouring the proton pumps were missing in nb8m delta. Nevertheless, nb8m delta still pumps protons at half the stoichiometry of the complete enzyme. Our results provide evidence that the membrane arm of complex I harbours two functionally distinct pump modules that are connected in series by the long helical transmission element recently identified by X-ray structural analysis.
Y1  - 2011
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/22498
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30-113551
SN  - 1545-7885
N1  - Copyright: © 2011 Dröse et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
VL  - 9
IS  - (8): e1001128
SP  - 1
EP  - 11
ER  -