Kritsiligkou, P., Chatzi, A., Charalampous, G., Mironov, A., Grant, C. M. and Tokatlidis, K. (2017) Unconventional targeting of a thiol peroxidase to the mitochondrial intermembrane space facilitates oxidative protein folding. Cell Reports, 18(11), pp. 2729-2741. (doi: 10.1016/j.celrep.2017.02.053) (PMID:28297675) (PMCID:PMC5368413)
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Abstract
Thiol peroxidases are conserved hydrogen peroxide scavenging and signaling molecules that contain redox-active cysteine residues. We show here that Gpx3, the major H2O2 sensor in yeast, is present in the mitochondrial intermembrane space (IMS), where it serves a compartment-specific role in oxidative metabolism. The IMS-localized Gpx3 contains an 18-amino acid N-terminally extended form encoded from a non-AUG codon. This acts as a mitochondrial targeting signal in a pathway independent of the hitherto known IMS-import pathways. Mitochondrial Gpx3 interacts with the Mia40 oxidoreductase in a redox-dependent manner and promotes efficient Mia40-dependent oxidative protein folding. We show that cells lacking Gpx3 have aberrant mitochondrial morphology, defective protein import capacity, and lower inner membrane potential, all of which can be rescued by expression of a mitochondrial-only form of Gpx3. Together, our data reveal a novel role for Gpx3 in mitochondrial redox regulation and protein homeostasis.
| Item Type: | Articles |
|---|---|
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Tokatlidis, Professor Kostas and Chatzi, Ms Afroditi |
| Authors: | Kritsiligkou, P., Chatzi, A., Charalampous, G., Mironov, A., Grant, C. M., and Tokatlidis, K. |
| College/School: | College of Medical Veterinary and Life Sciences > School of Molecular Biosciences |
| Journal Name: | Cell Reports |
| Publisher: | Elsevier (Cell Press) |
| ISSN: | 2211-1247 |
| ISSN (Online): | 2211-1247 |
| Published Online: | 14 March 2017 |
| Copyright Holders: | Copyright © 2017 The Authors |
| First Published: | First published in Cell Reports 18(11):2729-2741 |
| Publisher Policy: | Reproduced under a Creative Commons License |
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