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MBC in Press, published online ahead of print June 27, 2007
Mol. Biol. Cell 10.1091/mbc.E07-01-0088

A more recent version of this article appeared on September 1, 2007
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Submitted on January 31, 2007
Accepted on June 19, 2007

Multiple Hsp40 Chaperones Function in Tom70-dependent Mitochondrial Import

Melanie K. Bhangoo, Stefan Tzankov, Anna C.Y. Fan, Kurt Dejgaard, David Y. Thomas, and Jason C. Young

Department of Biochemistry, McGill University, Montreal, QC, H3G 1Y6, Canada

Monitoring Editor: Jeffrey Brodsky

Mitochondrial preproteins that are imported via the Tom70 receptor are complexed with cytosolic chaperones before targeting to the mitochondrial outer membrane. The Adenine Nucleotide Transporter (ANT) follows this pathway and its purified mature form is identical to the preprotein. Purified ANT was reconstituted with chaperones in reticulocyte lysate, and bound proteins were identified by mass spectrometry. In addition to Hsc70 and Hsp90, a specific subset of cochaperones were found, but no mitochondria-specific targeting factors. Interestingly, three different Hsp40-related J-domain proteins were identified: DJA1, DJA2 and DJA4. The DJAs bound preproteins to different extents through their C-terminal regions. DJA dominant negative mutants lacking the N-terminal J-domains impaired mitochondrial import. The mutants blocked the binding of Hsc70 to preprotein, but with varying efficiency. The DJAs also showed significant differences in activation of the Hsc70 ATPase and Hsc70-dependent protein refolding. In HeLa cells, the DJAs increased new protein folding and mitochondrial import, although to different extents. No single DJA was superior to the others in all aspects, but each had a profile of partial specialization. The Hsp90 cochaperones p23 and Aha1 also regulated Hsp90-preprotein interactions. We suggest that multiple cochaperones with similar yet partially specialized properties cooperate in optimal chaperone-preprotein complexes.


Address correspondence to: Jason C. Young (jason.young2{at}mcgill.ca)




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S. Tzankov, M. J. H. Wong, K. Shi, C. Nassif, and J. C. Young
Functional Divergence between Co-chaperones of Hsc70
J. Biol. Chem., October 3, 2008; 283(40): 27100 - 27109.
[Abstract] [Full Text] [PDF]




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