P016
Redox regulation of protein biogenesis in the
mitochondrial intermembrane space
Kostas Tokatlidis
University of Glasgow, Glasgow, UK
Protein import into mitochondria is fundamental for their
biogenesis and therefore critical for cell survival. Protein
biogenesis in the intermembrane space relies on the Mia40
pathway that orchestrates oxidative folding of proteins in this
mitochondrial compartment. The key components Mia40 and
Erv1 of this pathway are known and our recent work has focused
on the key molecular interactions underpinning this pathway.
However, the regulation of this process and its putative links to
redox homeostasis and redox signalling are still elusive. We find
that the Mia40 pathway is influenced by hydrogen peroxide and
that Hyr1/Gpx3, a thiol-peroxidase known to act as a redox-transducer in H2O2 signalling via YAP1 in the cytosol also interacts
with Mia40. Hyr1/Gpx3 has been recently shown to localise to
the intermembrane space (along with other redox -active proteins
like thioredoxin and thioredoxin reductase) in addition to its
localisation in the cytosol. These data support the existence of
a hydrogen peroxide sensing mechanism in the mitochondrial
intermembrane space. Such a machinery is likely to be involved
in redox regulation and oxidative stress response in this compartment and may additionally cross-talk with the intermembrane
space oxidative folding pathway.