Reactivation of protein aggregates by mortalin and Tid1-the human mitochondrial Hsp70 chaperone system.

Details

Serval ID
serval:BIB_8D2613088291
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Reactivation of protein aggregates by mortalin and Tid1-the human mitochondrial Hsp70 chaperone system.
Journal
Cell Stress and Chaperones
Author(s)
Iosefson O., Sharon S., Goloubinoff P., Azem A.
ISSN
1466-1268 (Electronic)
ISSN-L
1355-8145
Publication state
Published
Issued date
2012
Volume
17
Number
1
Pages
57-66
Language
english
Abstract
The mitochondrial 70-kDa heat shock protein (mtHsp70), also known in humans as mortalin, is a central component of the mitochondrial protein import motor and plays a key role in the folding of matrix-localized mitochondrial proteins. MtHsp70 is assisted by a member of the 40-kDa heat shock protein co-chaperone family named Tid1 and a nucleotide exchange factor. Whereas, yeast mtHsp70 has been extensively studied in the context of protein import in the mitochondria, and the bacterial 70-kDa heat shock protein was recently shown to act as an ATP-fuelled unfolding enzyme capable of detoxifying stably misfolded polypeptides into harmless natively refolded proteins, little is known about the molecular functions of the human mortalin in protein homeostasis. Here, we developed novel and efficient purification protocols for mortalin and the two spliced versions of Tid1, Tid1-S, and Tid1-L and showed that mortalin can mediate the in vitro ATP-dependent reactivation of stable-preformed heat-denatured model aggregates, with the assistance of Mge1 and either Tid1-L or Tid1-S co-chaperones or yeast Mdj1. Thus, in addition of being a central component of the protein import machinery, human mortalin together with Tid1, may serve as a protein disaggregating machine which, for lack of Hsp100/ClpB disaggregating co-chaperones, may carry alone the scavenging of toxic protein aggregates in stressed, diseased, or aging human mitochondria.
Pubmed
Web of science
Create date
05/01/2012 16:11
Last modification date
20/08/2019 14:51
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