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P 25 - Prof. Dr. Nikolaus Pfanner

Role of membrane contact sites in preprotein translocation into mitochondria



Prof. Dr. Nikolaus Pfanner

Institut für Biochemie und Molekularbologie, Universität Freiburg

Stefan-Meier-Str. 17

79104 Freiburg

Phone: +49 761 203-5224

Fax: +49 761 203-5261



Project Summary


Mitochondria possess a characteristic architecture with two membranes and two aqueous compartments. Nuclear-encoded precursor proteins are initially translocated into mitochondria via the general translocase of the outer membrane (TOM), yet subsequently follow different transport pathways to their specific intramitochondrial locations. Different views have been discussed about the role of contact sites between mitochondrial outer and inner membranes in preprotein translocation. We found that the TOM complex not only interacts with the presequence translocase of the inner membrane (TIM23) but also with the mitochondrial contact site and cristae organizing system (MICOS). The TOM-TIM23 supercomplex mediates import of cleavable preproteins, whereas the TOM-MICOS interaction promotes the import of cysteine-rich proteins via the mitochondrial intermembrane space import and assembly machinery (MIA). Little is known about the mechanism of cooperation between outer and inner membrane machineries. The goal of this project is to characterize molecular mechanisms, function and specificity of TOM-TIM23 and TOM-MICOS-MIA interactions. It will be analyzed how these dynamic membrane contact sites discriminate between different classes of precursor proteins and promote their translocation. We will study how preproteins with different signal sequences and post-translational modifications regulate protein transport machineries and their cooperation with the MICOS morphology machinery in a two-membrane-spanning network.

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