title: Protein oxidative folding in the intermembrane mitochondrial space: more than protein trafficking.
abstract: The process of oxidative folding in the intermembrane mitochondrial space (IMS) is an exciting field of research because folding is simultaneously coupled to protein translocation and functional regulation. Contrary to the endoplasmatic reticulum ER where several chaperones of the disulfide isomerase family exist, oxidative folding in the IMS is exclusively catalyzed by the oxoreductase Mia40 that recognizes a group of proteins with characteristic cysteine motifs organized in twin CX(3)C, twin CX(9)C or CX(2)C motifs. In this review, we discuss the structural and biochemical studies leading to our current understanding of the Mia40 pathway as well as the open questions on the field. In fact, despite significant advances, several key points on the Mia40 pathway remain to clarify namely on the molecular mechanism trough which substrate oxidative folding is catalyzed. This issue is receiving increasing attention since failures in the import, sorting and folding of mitochondrial proteins is related to an increasing number of debilitating human disorders.
authors.affiliation: Departament de Bioquímica i Biologia Molecular, Facultat de Ciències, Universitat Autònoma de Barcelona, E-08193 Bellaterra, Spain. hugofraga@gmail.com
authors.forename: Hugo
authors.initials: H
authors.lastname: Fraga
authors.forename: Salvador
authors.initials: S
authors.lastname: Ventura
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism / Q000502:physiology; D003579:Cytochrome Reductases / Q000737:chemistry / Q000378:metabolism / Q000502:physiology; D006801:Humans; D033681:Mitochondrial Membrane Transport Proteins / Q000737:chemistry / Q000378:metabolism / Q000502:physiology; D051336:Mitochondrial Membranes / Q000378:metabolism*; D000090622:Mitochondrial Precursor Protein Import Complex Proteins; D010084:Oxidation-Reduction; D050862:Oxidoreductases Acting on Sulfur Group Donors; D017510:Protein Folding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D021381:Protein Transport
chemical_list: C507282:CHCHD4 protein, human; D002352:Carrier Proteins; D033681:Mitochondrial Membrane Transport Proteins; D000090622:Mitochondrial Precursor Protein Import Complex Proteins; D003579:Cytochrome Reductases; C500897:GFER protein, human; D050862:Oxidoreductases Acting on Sulfur Group Donors