This Article Full Text Full Text (PDF) Other Versions of this Article: MCB.00007-08v1 28/13/4424    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Google Scholar Articles by Schiller, D. Articles by Craig, E. A. PubMed PubMed Citation Articles by Schiller, D. Articles by Craig, E. A.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, July 2008, p. 4424-4433, Vol. 28, No. 13
0270-7306/08/$08.00+0     doi:10.1128/MCB.00007-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Residues of Tim44 Involved in both Association with the Translocon of the Inner Mitochondrial Membrane and Regulation of Mitochondrial Hsp70 Tethering

Dirk Schiller, Yu Chin Cheng, Qinglian Liu, William Walter, and Elizabeth A. Craig^*

Department of Biochemistry, University of Wisconsin—Madison, Madison, Wisconsin 53706

Received 3 January 2008/ Returned for modification 5 March 2008/ Accepted 10 April 2008

Translocation of proteins from the cytosol across the mitochondrial inner membrane is driven by the action of the import motor, which is associated with the translocon on the matrix side of the membrane. It is well established that an essential peripheral membrane protein, Tim44, tethers mitochondrial Hsp70 (mtHsp70), the core of the import motor, to the translocon. This Tim44-mtHsp70 interaction, which can be recapitulated in vitro, is destabilized by binding of mtHsp70 to a substrate polypeptide. Here we report that the N-terminal 167-amino-acid segment of mature Tim44 is sufficient for both interaction with mtHsp70 and destabilization of a Tim44-mtHsp70 complex caused by client protein binding. Amino acid alterations within a 30-amino-acid segment affected both the release of mtHsp70 upon peptide binding and the interaction of Tim44 with the translocon. Our results support the idea that Tim44 plays multiple roles in mitochondrial protein import by recruiting Ssc1 and its J protein cochaperone to the translocon and coordinating their interactions to promote efficient protein translocation in vivo.

Published ahead of print on 21 April 2008.

Present address: Abbott Laboratories, 100 Abbott Park Road, Abbott Park, IL 60064.

Present address: Department of Biochemistry & Molecular Biophysics, Columbia University, 650 W. 168th St., New York, NY 10032.