Abstract:
:The intermembrane space of mitochondria accommodates the essential mitochondrial intermembrane space assembly (MIA) machinery that catalyzes oxidative folding of proteins. The disulfide bond formation pathway is based on a relay of reactions involving disulfide transfer from the sulfhydryl oxidase Erv1 to Mia40 and from Mia40 to substrate proteins. However, the substrates of the MIA typically contain two disulfide bonds. It was unclear what the mechanisms are that ensure that proteins are released from Mia40 in a fully oxidized form. In this work, we dissect the stage of the oxidative folding relay, in which Mia40 binds to its substrate. We identify dynamics of the Mia40-substrate intermediate complex. Our experiments performed in a native environment, both in organello and in vivo, show that Erv1 directly participates in Mia40-substrate complex dynamics by forming a ternary complex. Thus Mia40 in cooperation with Erv1 promotes the formation of two disulfide bonds in the substrate protein, ensuring the efficiency of oxidative folding in the intermembrane space of mitochondria.
journal_name
Mol Biol Celljournal_title
Molecular biology of the cellauthors
Böttinger L,Gornicka A,Czerwik T,Bragoszewski P,Loniewska-Lwowska A,Schulze-Specking A,Truscott KN,Guiard B,Milenkovic D,Chacinska Adoi
10.1091/mbc.E12-05-0358subject
Has Abstractpub_date
2012-10-01 00:00:00pages
3957-69issue
20eissn
1059-1524issn
1939-4586pii
mbc.E12-05-0358journal_volume
23pub_type
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