| Structural highlights
Function
MIA40_HUMAN Functions as chaperone and catalyzes the formation of disulfide bonds in substrate proteins, such as COX17. Required for the import and folding of small cysteine-containing proteins (small Tim) in the mitochondrial intermembrane space (IMS). Precursor proteins to be imported into the IMS are translocated in their reduced form into the mitochondria. The oxidized form of CHCHD4/MIA40 forms a transient intermolecular disulfide bridge with the reduced precursor protein, resulting in oxidation of the precursor protein that now contains an intramolecular disulfide bond and is able to undergo folding in the IMS. Reduced CHCHD4/MIA40 is then reoxidized by GFER/ERV1 via a disulfide relay system.[1] [2] [3] [4]
References
- ↑ Hofmann S, Rothbauer U, Muhlenbein N, Baiker K, Hell K, Bauer MF. Functional and mutational characterization of human MIA40 acting during import into the mitochondrial intermembrane space. J Mol Biol. 2005 Oct 28;353(3):517-28. PMID:16185709 doi:https://dx.doi.org/S0022-2836(05)01031-4
- ↑ Sztolsztener ME, Brewinska A, Guiard B, Chacinska A. Disulfide bond formation: sulfhydryl oxidase ALR controls mitochondrial biogenesis of human MIA40. Traffic. 2013 Mar;14(3):309-20. doi: 10.1111/tra.12030. Epub 2012 Dec 16. PMID:23186364 doi:https://dx.doi.org/10.1111/tra.12030
- ↑ Banci L, Bertini I, Cefaro C, Ciofi-Baffoni S, Gallo A, Martinelli M, Sideris DP, Katrakili N, Tokatlidis K. MIA40 is an oxidoreductase that catalyzes oxidative protein folding in mitochondria. Nat Struct Mol Biol. 2009 Feb;16(2):198-206. Epub 2009 Feb 1. PMID:19182799 doi:10.1038/nsmb.1553
- ↑ Banci L, Bertini I, Cefaro C, Cenacchi L, Ciofi-Baffoni S, Felli IC, Gallo A, Gonnelli L, Luchinat E, Sideris D, Tokatlidis K. Molecular chaperone function of Mia40 triggers consecutive induced folding steps of the substrate in mitochondrial protein import. Proc Natl Acad Sci U S A. 2010 Nov 8. PMID:21059946 doi:10.1073/pnas.1010095107
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