NDUFAF5 hydroxylates NDUFS7 at an early stage in the assembly of human complex I.

TitleNDUFAF5 hydroxylates NDUFS7 at an early stage in the assembly of human complex I.
Publication TypeJournal Article
Year of Publication2016
AuthorsRhein, VF, Carroll, J, Ding, S, Fearnley, IM, Walker, JE
JournalJ Biol Chem
Volume291
Start Page14851
Pagination14851-60
Date Published2016 May 18
ISSN1083-351X
Abstract

Complex I (NADH ubiquinone oxidoreductase) in mammalian mitochondria is an L-shaped assembly of 45 proteins. One arm lies in the inner membrane and the other extends about 100 Å into the matrix of the organelle. The extrinsic arm contains binding sites for NADH, the primary electron acceptor FMN, and seven iron-sulfur clusters that form a pathway for electrons linking FMN to the terminal electron acceptor, ubiquinone, which is bound in a tunnel in the region of the junction between the arms. The membrane arm contains four antiporter-like domains, energetically coupled to the quinone site and involved in pumping protons from the matrix into the intermembrane space contributing to the proton motive force. Seven of the subunits, forming the core of the membrane arm, are translated from mitochondrial genes, and the remaining subunits, the products of nuclear genes, are imported from the cytosol. Their assembly is coordinated by at least thirteen extrinsic assembly factor proteins that are not part of the fully assembled complex. They assist in insertion of co-factors and in building up the complex from smaller sub-assemblies. One such factor, NDUFAF5, belongs to the family of seven-β-strand S-adenosylmethionine-dependent methyltransferases. However, similar to another family member, RdmB, it catalyzes the introduction of a hydroxyl group into an arginine residue, in the case of NDUFAF5, into Arg-73 in the NDUFS7 subunit of human complex I. This modification occurs early in the pathway of assembly of complex I, before the formation of the juncture between peripheral and membrane arms.

DOI10.1074/jbc.M116.734970
Alternate JournalJ. Biol. Chem.
Citation Key10.1074/jbc.M116.734970
PubMed ID27226634