A structural model for FOXRED1, an FAD-dependent oxidoreductase necessary for NADH: Ubiquinone oxidoreductase (complex I) assembly

Mitochondrion. 2015 May:22:9-16. doi: 10.1016/j.mito.2015.02.008. Epub 2015 Mar 9.

Abstract

The biogenesis of mitochondrial respiratory chain components is complex. Mammalian complex I (NADH:ubiquinone oxidoreductase) contains 44 different subunits, an FMN and seven iron-sulfur centers. Its assembly involves at least twelve additional proteins, called assembly factors. One of these is FOXRED1, a 486-amino acid FAD-dependent oxidoreductase. FOXRED1 is a member of the d-amino acid oxidase (DAO) family. A structural model of FOXRED1 reveals a large substrate-binding cavity and a putative oxygen-binding site. These features strongly suggest that FOXRED1 is catalytically active as an oxidoreductase. A metabolic role for FOXRED1 in the biogenesis of complex I should be considered.

Keywords: Flavoprotein; Leigh syndrome; Mitochondrial disease; NADH:ubiquinone oxidoreductase; Oxidase; Structural model.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Catalytic Domain
  • Flavin-Adenine Dinucleotide / chemistry*
  • Flavin-Adenine Dinucleotide / metabolism*
  • Humans
  • Models, Molecular
  • Molecular Chaperones / chemistry*
  • Molecular Chaperones / metabolism*
  • Molecular Sequence Data
  • NAD / metabolism*
  • Oxidoreductases / chemistry*
  • Oxidoreductases / metabolism*
  • Sequence Alignment

Substances

  • FOXRED1 protein, human
  • Molecular Chaperones
  • NAD
  • Flavin-Adenine Dinucleotide
  • Oxidoreductases