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Vol. 19, Issue 6, 2642-2649, June 2008

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Mitochondrial Protein Import Motor: Differential Role of Tim44 in the Recruitment of Pam17 and J-Complex to the Presequence Translocase

Dana P. Hutu^*,,, Bernard Guiard, Agnieszka Chacinska^*, Dorothea Becker^*,, Nikolaus Pfanner^*, Peter Rehling^*,, and Martin van der Laan^*

*Institut für Biochemie und Molekularbiologie, ZBMZ and Fakultät für Biologie, Universität Freiburg, D-79104 Freiburg, Germany; Abteilung für Biochemie II, Universität Göttingen, D-37073 Göttingen, Germany; and Centre de Génétique Moléculaire, CNRS, 91190 Gif-sur-Yvette, France

Submitted December 10, 2007; Revised March 24, 2008; Accepted April 2, 2008
Monitoring Editor: Benjamin Glick

The presequence translocase of the mitochondrial inner membrane (TIM23 complex) mediates the import of preproteins with amino-terminal presequences. To drive matrix translocation the TIM23 complex recruits the presequence translocase-associated motor (PAM) with the matrix heat shock protein 70 (mtHsp70) as central subunit. Activity and localization of mtHsp70 are regulated by four membrane-associated cochaperones: the adaptor protein Tim44, the stimulatory J-complex Pam18/Pam16, and Pam17. It has been proposed that Tim44 serves as molecular platform to localize mtHsp70 and the J-complex at the TIM23 complex, but it is unknown how Pam17 interacts with the translocase. We generated conditional tim44 yeast mutants and selected a mutant allele, which differentially affects the association of PAM modules with TIM23. In tim44-804 mitochondria, the interaction of the J-complex with the TIM23 complex is impaired, whereas unexpectedly the binding of Pam17 is increased. Pam17 interacts with the channel protein Tim23, revealing a new interaction site between TIM23 and PAM. Thus, the motor PAM is composed of functional modules that bind to different sites of the translocase. We suggest that Tim44 is not simply a scaffold for binding of motor subunits but plays a differential role in the recruitment of PAM modules to the inner membrane translocase.

Address correspondence to: Nikolaus Pfanner (nikolaus.pfanner{at}biochemie.uni-freiburg.de) or Peter Rehling (peter.rehling{at}medizin.uni-goettingen.de)

Abbreviations used: p, proton-motive force; J-complex, Pam18-Pam16 complex of mitochondria; mtHsp70, mitochondrial heat shock protein 70; PAM, presequence translocase-associated motor; TIM, presequence translocase of inner mitochondrial membrane

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