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SUMMARY:Rescuing mitochondria in peril under oxidative stress - Professor 
 Kostas Tokatlidis | University of Glasgow
DTSTART:20221123T150000Z
DTEND:20221123T160000Z
UID:TALK165577@talks.cam.ac.uk
CONTACT:72232
DESCRIPTION:Mitochondria need to have defence mechanisms to respond to del
 eterious stresses like oxidative stress that can damage proteins\, DNA and
  lipids. Cellular H2O2 homeostasis and signalling in S. cerevisiae are med
 iated by a specific H2O2-inducible transcriptional response engaging the Y
 AP1 transcription factor. Activation of YAP1 in the cytosol depends on the
  thiol peroxidase Gpx3/Orp1. We have found that\, upon H2O2 stress\, Gpx3 
 activates another\, YAP1-independent and compartment-specific defence path
 way in mitochondria. This is initiated by a stress-dependent mitochondrial
  targeting of Gpx3 guided by an N-terminal targeting peptide that is appen
 ded to the protein by alternative translation in the cytosol. This extende
 d form of Gpx3 follows a novel import pathway that is independent of outer
  membrane import receptors\, ATP hydrolysis or the inner membrane potentia
 l and can still operate in dysfunctional mitochondria with a damaged inner
  membrane. Gpx3 in the IMS engages in both protein-protein and protein-lip
 id interactions facilitating optimal operation of the oxidative folding MI
 A machinery and protecting the inner mitochondrial membrane from oxidative
  damage. We have found that\, under stress conditions\, Gpx3 allows mitoch
 ondria to bypass the disulfide relay mechanism that is thought until now t
 o be essential for the function of Mia40. This stress-induced bypass rescu
 es the biogenesis process in the mitochondrial IMS\, which would otherwise
  be blocked. The molecular interactions underpinning this new pathway are 
 important for optimal mitochondrial quality control\, proteostasis and cel
 l survival.
LOCATION:MRC MBU\, Level 7 Lecture Theatre\, The Keith Peters Building\, C
 B2 0XY
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