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SUMMARY:'Disulfide bond formation in biogenesis of mitochondrial proteins'
  - Professor Agnieszka Chacinska\, International Institute of Molecular an
 d Cell Biology\, Poland
DTSTART:20101215T150000Z
DTEND:20101215T160000Z
UID:TALK28395@talks.cam.ac.uk
CONTACT:Penny Peck
DESCRIPTION:Mitochondria play a critical role in cellular metabolism and h
 ave also been strongly implicated in apoptosis\, ageing and a number of di
 seases. Biogenesis of mitochondrial proteins is a multi-step process that\
 , beside synthesis\, involves their subsequent transport\, folding into th
 eir native conformation\, diverse maturation events and associations with 
 partner proteins to form functional complexes. We have discovered a novel 
 MIA pathway (Mitochondrial Intermembrane Space Assembly) dedicated to the 
 biogenesis of intermembrane space proteins. A hallmark of this pathway is 
 the regulated transfer of disulfide bonds\, a process that had not been pr
 eviously described in mitochondria. The MIA pathway represents a novel dis
 ulfide-transferring system to control the vectorial translocation of prote
 ins into mitochondria. Mia40\, one of the essential components of this pat
 hway\, acts in a receptor-like manner. It shows a striking selectivity in 
 the protein substrate recognition\, thereby dictating substrate entry to t
 he MIA pathway. This mode of action stands in contrast to mechanisms utili
 zed by other\, rather promiscuous\, disulfide transferring enzymes such as
  DsbA and PDI. Furthermore\, a mode of the cooperation between Mia40 and t
 he sulfhydryl oxidase Erv1 is unique. We propose that the simultaneous ass
 ociation of Mia40\, Erv1 and a substrate protein in the ternary complex al
 lows the efficient transfer of multiple disulfide bonds into substrate pro
 teins. These findings have put in place novel concepts for the biogenesis 
 of mitochondrial proteins and for the generation and transfer of disulfide
  bonds and their impact on protein compartmentalization and organelle func
 tioning.
LOCATION:Sackler Lecture Theatre (Level 7)\, Wellcome Trust/MRC Building\,
  Addenbrooke's Site
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