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Popov-Celeketic, Dusan (2007): Dynamic Regulation of Function of the Mitochondrial TIM23 Preprotein Translocase. Dissertation, LMU München: Fakultät für Biologie



The vast majority of mitochondrial proteins are synthesized on cytosolic ribosomes in the form of precursor proteins and subsequently imported into mitochondria through the concerted action of the translocases present in the outer and the inner membrane. The TIM23 complex (translocase of the inner membrane) mediates translocation of precursor proteins across or their insertion into the mitochondrial inner membrane in a membrane potential and ATP-dependent manner. The TIM23 complex consists of eight essential subunits that can be assigned to two operationally defined parts: the membrane embedded protein conducting channel with the receptor and the import motor associated with the channel at the matrix side of the inner membrane. The present study was undertaken to gain insight into the dynamics of the TIM23 translocase during import of different types of preproteins. A previously uncharacterized protein component of the TIM23 translocase was identified and termed Tim21. Results presented in this study demonstrate that the TIM23 translocase switches between translocation mode that facilitates import of proteins into the matrix and insertion mode that allows lateral sorting of proteins into the lipid bilayer. The TIM23 translocase adopts different conformations in its various states of activity: when it was empty, when it inserted preproteins into the inner membrane and when it translocated preproteins targeted to the matrix. The interconversion of the TIM23 translocase between the functional states occurs primarily by conformational changes of the essential components, whereas non-essential components Tim21 and Pam17 are responsible for the fine tuning of these processes. A hypothesis that describes the behavior of the TIM23 translocase is presented.