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Kmita 2015 Proc Natl Acad Sci U S A

From Bioblast
Publications in the MiPMap
Kmita K, Wirth C, Warnau J, Guerrero-Castillo S, Hunte C, Hummer G, Kaila VR, Zwicker K, Brandt U, Zickermann V (2015) Accessory NUMM (NDUFS6) subunit harbors a Zn-binding site and is essential for biogenesis of mitochondrial complex I.

ยป Proc Natl Acad Sci U S A 112:5685-90. PMID: 25902503 Open Access

Kmita Katarzyna, Wirth Christophe, Warnau Judith, Guerrero-Castillo Sergio, Hunte Carola, Hummer Gerhard, Kaila Ville RI, Zwicker Klaus, Brandt Ulrich, Zickermann Volker (2015) Proc Natl Acad Sci U S A

Abstract: Mitochondrial proton-pumping NADH:ubiquinone oxidoreductase (respiratory complex I) comprises more than 40 polypeptides and contains eight canonical FeS clusters. The integration of subunits and insertion of cofactors into the nascent complex is a complicated multistep process that is aided by assembly factors. We show that the accessory NUMM subunit of complex I (human NDUFS6) harbors a Zn-binding site and resolve its position by X-ray crystallography. Chromosomal deletion of the NUMM gene or mutation of Zn-binding residues blocked a late step of complex I assembly. An accumulating assembly intermediate lacked accessory subunit N7BM (NDUFA12), whereas a paralog of this subunit, the assembly factor N7BML (NDUFAF2), was found firmly bound instead. EPR spectroscopic analysis and metal content determination after chromatographic purification of the assembly intermediate showed that NUMM is required for insertion or stabilization of FeS cluster N4. โ€ข Keywords: FeS cluster, NDUFA12, NDUFAF2, Assembly, Metal protein โ€ข Bioblast editor: Plangger M

Labels: MiParea: mt-Structure;fission;fusion 

Enzyme: Complex I