title: Targeting and maturation of Erv1/ALR in the mitochondrial intermembrane space.
abstract: The interaction of Mia40 with Erv1/ALR is central to the oxidative protein folding in the intermembrane space of mitochondria (IMS) as Erv1/ALR oxidizes reduced Mia40 to restore its functional state. Here we address the role of Mia40 in the import and maturation of Erv1/ALR. The C-terminal FAD-binding domain of Erv1/ALR has an essential role in the import process by creating a transient  intermolecular disulfide bond with Mia40. The action of Mia40 is selective for the formation of both intra and intersubunit structural disulfide bonds of Erv1/ALR, but the complete maturation process requires additional binding of FAD. Both of these events must follow a specific sequential order to allow Erv1/ALR to reach the fully functional state, illustrating a new paradigm for protein maturation in the IMS.
authors.affiliation: Institute of Molecular Biology and Biotechnology, Foundation for Research and Technology Hellas, Heraklion, Crete, Greece.
authors.forename: Emmanouela
authors.initials: E
authors.lastname: Kallergi
authors.forename: Maria
authors.initials: M
authors.lastname: Andreadaki
authors.forename: Paraskevi
authors.initials: P
authors.lastname: Kritsiligkou
authors.forename: Nitsa
authors.initials: N
authors.lastname: Katrakili
authors.forename: Charalambos
authors.initials: C
authors.lastname: Pozidis
authors.forename: Kostas
authors.initials: K
authors.lastname: Tokatlidis
authors.forename: Lucia
authors.initials: L
authors.lastname: Banci
authors.forename: Ivano
authors.initials: I
authors.lastname: Bertini
authors.forename: Chiara
authors.initials: C
authors.lastname: Cefaro
authors.forename: Simone
authors.initials: S
authors.lastname: Ciofi-Baffoni
authors.forename: Karolina
authors.initials: K
authors.lastname: Gajda
authors.forename: Riccardo
authors.initials: R
authors.lastname: Peruzzini
mesh_terms: D003579:Cytochrome Reductases / Q000378:metabolism*; D004220:Disulfides; D005182:Flavin-Adenine Dinucleotide / Q000378:metabolism*; D006801:Humans; D033681:Mitochondrial Membrane Transport Proteins; D051336:Mitochondrial Membranes / Q000378:metabolism*; D000090622:Mitochondrial Precursor Protein Import Complex Proteins; D050862:Oxidoreductases Acting on Sulfur Group Donors; D017510:Protein Folding; D021381:Protein Transport
chemical_list: C507282:CHCHD4 protein, human; D004220:Disulfides; D033681:Mitochondrial Membrane Transport Proteins; D000090622:Mitochondrial Precursor Protein Import Complex Proteins; D005182:Flavin-Adenine Dinucleotide; D003579:Cytochrome Reductases; C500897:GFER protein, human; D050862:Oxidoreductases Acting on Sulfur Group Donors