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2017 ; 18
(11
): 2729-2741
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Unconventional Targeting of a Thiol Peroxidase to the Mitochondrial Intermembrane
Space Facilitates Oxidative Protein Folding
#MMPMID28297675
Kritsiligkou P
; Chatzi A
; Charalampous G
; Mironov A Jr
; Grant CM
; Tokatlidis K
Cell Rep
2017[Mar]; 18
(11
): 2729-2741
PMID28297675
show ga
Thiol peroxidases are conserved hydrogen peroxide scavenging and signaling
molecules that contain redox-active cysteine residues. We show here that Gpx3,
the major H(2)O(2) 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.