TY  - JOUR
A1  - Kashani-Poor, Noushin
A1  - Zwicker, Klaus
A1  - Kerscher, Stefan
A1  - Brandt, Ulrich
T1  - A central functional role for the 49-kDa subunit within the catalytic core of mitochondrial complex I
T2  - Journal of biological chemistry
N2  - We have analyzed a series of eleven mutations in the 49-kDa protein of mitochondrial complex I (NADH:ubiquinone oxidoreductase) from Yarrowia lipolytica to identify functionally important domains in this central subunit. The mutations were selected based on sequence homology with the large subunit of [NiFe] hydrogenases. None of the mutations affected assembly of complex I, all decreased or abolished ubiquinone reductase activity. Several mutants exhibited decreased sensitivities toward ubiquinone-analogous inhibitors. Unexpectedly, seven mutations affected the properties of iron-sulfur cluster N2, a prosthetic group not located in the 49-kDa subunit. In three of these mutants cluster N2 was not detectable by electron-paramagnetic resonance spectroscopy. The fact that the small subunit of hydrogenase is homologous to the PSST subunit of complex I proposed to host cluster N2 offers a straightforward explanation for the observed, unforeseen effects on this iron-sulfur cluster. We propose that the fold around the hydrogen reactive site of [NiFe] hydrogenase is conserved in the 49-kDa subunit of complex I and has become part of the inhibitor and ubiquinone binding region. We discuss that the fourth ligand of iron-sulfur cluster N2 missing in the PSST subunit may be provided by the 49-kDa subunit.
Y1  - 2021
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/75980
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-759805
SN  - 0021-9258
VL  - 276
IS  - 26
SP  - 24082
EP  - 24087
PB  - American Society for Biochemistry and Molecular Biology Publications
CY  - Bethesda, Md
ER  -