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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Abstract
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) |
|---|---|
| Status: | Published |
| Refereed: | Yes |
| 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 > School of Molecular Biosciences |
| Journal Name: | Antioxidants and Redox Signaling |
| Publisher: | Mary Ann Liebert |
| ISSN: | 1523-0864 |
| ISSN (Online): | 1557-7716 |
| Published Online: | 03 October 2012 |
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