Accessory NUMM (NDUFS6) subunit harbors a Zn-binding site and is essential for biogenesis of mitochondrial complex I.

20.04.2015

Kmita K, Wirth C, Warnau J, Guerrero-Castillo S, Hunte C, Hummer G, Kaila VR, Zwicker K, Brandt U, Zickermann V.

Proc Natl Acad Sci U S A. 2015;112(18):5685-90

Proc Natl Acad Sci U S A.            online article

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 its assembly defects. The concerted assembly of more than 40 subunits and the insertion of cofactors is aided by specific chaperones. Here a zinc (Zn)-binding site with a role in complex I biogenesis was described. The Zn-binding site was identified in the accessory subunit NUMM of complex I and its position in the structure was resolved by X-ray crystallography. Mutation of Zn-binding residues blocked a late step of complex I assembly so that assembly intermediates accumulated. EPR spectroscopic analysis and metal content determination of the purified assembly intermediate showed that NUMM is required for insertion or stabilization of FeS cluster N4.