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Folding and Biogenesis of Mitochondrial Small Tim Proteins
Manchester Institute of Biotechnology, Faculty of Life Sciences, University of Manchester, 131 Princess Street, Manchester M1 7DN, UK
These authors contributed equally to this work.
* Author to whom correspondence should be addressed.
Received: 28 June 2013; in revised form: 1 August 2013 / Accepted: 7 August 2013 / Published: 13 August 2013
Abstract: Correct and timely folding is critical to the function of all proteins. The importance of this is illustrated in the biogenesis of the mitochondrial intermembrane space (IMS) “small Tim” proteins. Biogenesis of the small Tim proteins is regulated by dedicated systems or pathways, beginning with synthesis in the cytosol and ending with assembly of individually folded proteins into functional complexes in the mitochondrial IMS. The process is mostly centered on regulating the redox states of the conserved cysteine residues: oxidative folding is crucial for protein function in the IMS, but oxidized (disulfide bonded) proteins cannot be imported into mitochondria. How the redox-sensitive small Tim precursor proteins are maintained in a reduced, import-competent form in the cytosol is not well understood. Recent studies suggest that zinc and the cytosolic thioredoxin system play a role in the biogenesis of these proteins. In the IMS, the mitochondrial import and assembly (MIA) pathway catalyzes both import into the IMS and oxidative folding of the small Tim proteins. Finally, assembly of the small Tim complexes is a multistep process driven by electrostatic and hydrophobic interactions; however, the chaperone function of the complex might require destabilization of these interactions to accommodate the substrate. Here, we review how folding of the small Tim proteins is regulated during their biogenesis, from maintenance of the unfolded precursors in the cytosol, to their import, oxidative folding, complex assembly and function in the IMS.
Keywords: oxidative protein folding; small Tim; protein import; mitochondrial intermembrane space; AAC
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Ceh-Pavia, E.; Spiller, M.P.; Lu, H. Folding and Biogenesis of Mitochondrial Small Tim Proteins. Int. J. Mol. Sci. 2013, 14, 16685-16705.
Ceh-Pavia E, Spiller MP, Lu H. Folding and Biogenesis of Mitochondrial Small Tim Proteins. International Journal of Molecular Sciences. 2013; 14(8):16685-16705.
Ceh-Pavia, Efrain; Spiller, Michael P.; Lu, Hui. 2013. "Folding and Biogenesis of Mitochondrial Small Tim Proteins." Int. J. Mol. Sci. 14, no. 8: 16685-16705.