A disulfide relay system in mitochondria.
In this issue of Cell, show that there is a disulfide relay system in the intermembrane space (IMS) of mitochondria that is comprised of the proteins Mia40 and Erv1. This disulfide relay system promotes the import and oxidative folding of proteins. Oxidized Mia40 traps newly imported proteins through mixed disulfide bridges. Subsequent isomerization of these disulfide bridges allows the imported protein to be folded in the IMS. The reduced Mia40 generated is then reoxidized by the sulfhydryl oxidase Erv1, promoting the next round of disulfide exchange. The new work clarifies the molecular function of Mia40 and reveals Mia40 to be the first physiological substrate for the FAD-linked Erv1.
IMBB-FORTH, Vasilika Vouton, GR-711 10 Heraklion-Crete, Greece.
Kostas
K
Tokatlidis
D000818:Animals; D004220:Disulfides / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D007425:Intracellular Membranes / Q000378:metabolism*; D008928:Mitochondria / Q000378:metabolism*; D033681:Mitochondrial Membrane Transport Proteins / Q000737:chemistry / Q000378:metabolism*; D000090622:Mitochondrial Precursor Protein Import Complex Proteins; D024101:Mitochondrial Proteins / Q000737:chemistry / Q000378:metabolism*; D010084:Oxidation-Reduction; D050862:Oxidoreductases Acting on Sulfur Group Donors; D017510:Protein Folding; D021381:Protein Transport / Q000502:physiology; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000378:metabolism*
D004220:Disulfides; C495320:MIA40 protein, S cerevisiae; D033681:Mitochondrial Membrane Transport Proteins; D000090622:Mitochondrial Precursor Protein Import Complex Proteins; D024101:Mitochondrial Proteins; D029701:Saccharomyces cerevisiae Proteins; D050862:Oxidoreductases Acting on Sulfur Group Donors; C073790:ERV1 protein, S cerevisiae