Untersuchungen zur Proteintranslokation über die innere Mitochondrienmembran - Regulation der Aktivität des Proteinimportmotors

线粒体对真核细胞的能量代谢至关重要。虽然它们有自己的遗传装置，但绝大多数线粒体酶是在细胞质中作为前体合成的，必须通过内膜的前序转位酶。前蛋白的易位是通过输入马达的组成部分Tim44、Pam18、Pam16、Mge1和mtHsp70的调控和协调作用完成的。外周膜蛋白Tim44将线粒体伴侣蛋白mtHsp70（酵母中的Ssc1）拴在进口通道的出口处，在那里它与进入的多肽链结合。易位是通过mtHsp70连续结合到Tim44和肽底物的循环实现的。尽管Tim44:mtHsp70相互作用在蛋白质进口中起着核心作用，但人们对这种调节蛋白相互作用的分子机制知之甚少。为了阐明Tim44如何参与蛋白质易位，将对Tim44进行遗传、生化、生物物理和结构分析，以了解Tim44:mtHsp70相互作用在蛋白质进入线粒体基质中的机制和调控。

Mitochondria are essential for the energy metabolism of the eukaryotic cell. Although they contain their own genetic apparatus, the vast majority of mitochondrial enzymes are synthesized as precursors in the cytosol and must pass through the presequence translocase of the inner membrane. Translocation of preproteins is accomplished by a regulated and concerted action of the components of the import motor, namely Tim44, Pam18, Pam16, Mge1 and mtHsp70. The peripheral membrane protein Tim44 tethers the mitochondrial chaperone mtHsp70 (Ssc1 in yeast) to the exit of the import channel where it binds to the incoming polypeptide chain. Translocation is achieved by cycles of consecutive binding of mtHsp70 to Tim44 and to the peptide substrate. Despite the central role of the Tim44:mtHsp70 interaction in protein import little is known about the molecular mechanism of that regulatory protein protein interaction. To elucidate how Tim44 is involved in protein translocation, genetic, biochemical, biophysical and structural analyses of Tim44 will be carried out to understand the mechanism and the regulation of the Tim44:mtHsp70 interaction in protein import into the mitochondrial matix.