The mitochondrial intermembrane space: a hub for oxidative folding linked to protein biogenesis

Chatzi, A. and Tokatlidis, K. (2013) The mitochondrial intermembrane space: a hub for oxidative folding linked to protein biogenesis. Antioxidants and Redox Signaling, 19(1), pp. 54-62. (doi:10.1089/ars.2012.4855) (PMID:22901034)

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Significance: The introduction of disulfide bonds in proteins of the mitochondrial intermembrane space (IMS) is fundamental for their folding and assembly. This oxidative folding process depends on the disulfide donor/ import receptor Mia40 and the flavin adenine dinucleotide oxidase Erv1 and concerns proteins involved in mitochondrial biogenesis, respiratory complex assembly, and metal transfer. Recent Advances: The recently determined structural basis of the interaction between Mia40 and some substrates provides a framework for the electron transfer process. A possible proofreading role for the cellular reductant glutathione has been proposed, while other studies suggest the association of Mia40 and Erv1 in dynamic multiprotein complexes in the IMS. Critical Issues: The association of Mia40 with Erv1 and substrates in large multiprotein complexes is critical. Completion of substrate folding by additional disulfide bonds after initial binding to Mia40 remains unclear. Furthermore, a more general role for Mia40 in recognizing substrates targeted to other compartments, or even without specific cysteine motifs, remains an intriguing possibility. Future Directions: Dissecting a regulatory role of intramitochondrial protein complex organization and small redox-active molecules will be crucial for understanding oxidative folding in the IMS. This should have an impact on the physiology of human cells, as disease-linked mutations of key components of this process have been manifested, and their expression in stem cells appears crucial for development.

Item Type:Articles (Other)
Glasgow Author(s) Enlighten ID:Tokatlidis, Professor Kostas and Chatzi, Ms Afroditi
Authors: Chatzi, A., and Tokatlidis, K.
College/School:College of Medical Veterinary and Life Sciences > Institute of Molecular Cell and Systems Biology
Journal Name:Antioxidants and Redox Signaling
Publisher:Mary Ann Liebert
ISSN (Online):1557-7716
Published Online:03 October 2012

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