A dual role for mitochondrial heat shock protein 70 in membrane translocation of preproteins - PubMed (original) (raw)
Comparative Study
A dual role for mitochondrial heat shock protein 70 in membrane translocation of preproteins
B D Gambill et al. J Cell Biol. 1993 Oct.
Abstract
The role of mitochondrial 70-kD heat shock protein (mt-hsp70) in protein translocation across both the outer and inner mitochondrial membranes was studied using two temperature-sensitive yeast mutants. The degree of polypeptide translocation into the matrix of mutant mitochondria was analyzed using a matrix-targeted preprotein that was cleaved twice by the processing peptidase. A short amino-terminal segment of the preprotein (40-60 amino acids) was driven into the matrix by the membrane potential, independent of hsp70 function, allowing a single cleavage of the presequence. Artificial unfolding of the preprotein allowed complete translocation into the matrix in the case where mutant mt-hsp70 had detectable binding activity. However, in the mutant mitochondria in which binding to mt-hsp70 could not be detected the mature part of the preprotein was only translocated to the intermembrane space. We propose that mt-hsp70 fulfills a dual role in membrane translocation of preproteins. (a) Mt-hsp70 facilitates unfolding of the polypeptide chain for translocation across the mitochondrial membranes. (b) Binding of mt-hsp70 to the polypeptide chain is essential for driving the completion of transport of a matrix-targeted preprotein across the inner membrane. This second role is independent of the folding state of the preprotein, thus identifying mt-hsp70 as a genuine component of the inner membrane translocation machinery. Furthermore we determined the sites of the mutations and show that both a functional ATPase domain and ATP are needed for mt-hsp70 to bind to the polypeptide chain and drive its translocation into the matrix.
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References
- Eur J Biochem. 1984 Nov 2;144(3):581-8 - PubMed
- Mol Cell Biol. 1992 May;12(5):2186-92 - PubMed
- Cell. 1986 Jul 18;46(2):291-300 - PubMed
- FEBS Lett. 1986 Dec 15;209(2):152-6 - PubMed
- J Biol Chem. 1987 Jan 15;262(2):746-51 - PubMed
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