Display Settings:


Send to:

Choose Destination
See comment in PubMed Commons below
ACS Chem Biol. 2014 Sep 19;9(9):2049-57. doi: 10.1021/cb500408n. Epub 2014 Jul 10.

Mia40 is optimized for function in mitochondrial oxidative protein folding and import.

Author information

  • 1Laboratorium für Biochemie und Bayreuther Zentrum für Molekulare Biologie, Universität Bayreuth , 95440 Bayreuth, Germany.


Mia40 catalyzes oxidative protein folding in mitochondria. It contains a unique catalytic CPC dithiol flanked by a hydrophobic groove, and unlike other oxidoreductases, it forms long-lived mixed disulfides with substrates. We show that this distinctive property originates neither from particular properties of mitochondrial substrates nor from the CPC motif of Mia40. The catalytic cysteines of Mia40 display unusually low chemical reactivity, as expressed in conventional pK values and reduction potentials. The stability of the mixed disulfide intermediate is coupled energetically with hydrophobic interactions between Mia40 and the substrate. Based on these properties, we suggest a mechanism for Mia40, where the hydrophobic binding site is employed to select a substrate thiol for forming the initial mixed disulfide. Its long lifetime is used to retain partially folded proteins in the mitochondria and to direct folding toward forming the native disulfide bonds.

[PubMed - in process]
PubMed Commons home

PubMed Commons

How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for American Chemical Society
    Loading ...
    Write to the Help Desk