Int. J. Mol. Sci. 2013, 14(8), 16685-16705; doi:10.3390/ijms140816685

Folding and Biogenesis of Mitochondrial Small Tim Proteins

email, email and * email
Received: 28 June 2013; in revised form: 1 August 2013 / Accepted: 7 August 2013 / Published: 13 August 2013
(This article belongs to the Special Issue Protein Folding 2015)
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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
PDF Full-text Download PDF Full-Text [1091 KB, uploaded 19 June 2014 05:04 CEST]

Export to BibTeX |

MDPI and ACS Style

Ceh-Pavia, E.; Spiller, M.P.; Lu, H. Folding and Biogenesis of Mitochondrial Small Tim Proteins. Int. J. Mol. Sci. 2013, 14, 16685-16705.

AMA Style

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.

Chicago/Turabian Style

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.

Int. J. Mol. Sci. EISSN 1422-0067 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert