imprint:
Proceedings of the National Academy of Sciences, 2015
Published in:Proceedings of the National Academy of Sciences
Language:
English
DOI:
10.1073/pnas.1424353112
ISSN:
0027-8424;
1091-6490
Origination:
Footnote:
Description:
<jats:title>Significance</jats:title>
<jats:p>Respiratory complex I is the largest membrane protein complex in mitochondria and has a central function in energy metabolism. Numerous human diseases are linked with complex I dysfunction or assembly defects. The concerted assembly of more than 40 subunits and the insertion of cofactors is aided by specific chaperones. In addition to eight FeS clusters, complex I comprises a Zn-binding site of unknown function. Combining X-ray structural analysis of complex I crystals with quantum chemical modeling and proteomic and spectroscopic analysis of a purified assembly intermediate, we show that accessory subunit NUMM (human ortholog NDUFS6) binds Zn at the interface of two functional modules of the enzyme complex and is required for a specific step of complex I biogenesis.</jats:p>