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SUMMARY:Physio-pathology of mitochondrial complex III assembly - Dr Erika 
 Fernandez-Vizarra
DTSTART:20121017T140000Z
DTEND:20121017T150000Z
UID:TALK40758@talks.cam.ac.uk
CONTACT:Penny Peck
DESCRIPTION:Despite its central role in oxidative phosphorylation and othe
 r metabolic pathways\, there are many aspects of mammalian mitochondrial C
 omplex III (CIII) biogenesis that are still unknown. Most of the current k
 nowledge about how CIII is assembled has been obtained by studying the yea
 st S. cerevisiae\, which is a good model due to the enzyme’s conserved s
 tructure. However\, there are important differences between yeast and mamm
 als concerning mitochondrial biogenesis\, which underscore the necessity t
 o study the process in mammalian mitochondria to properly understand it. T
 wo main aspects of CIII assembly have been analyzed by using human and mou
 se systems: 1) how the subunits are brought together to give rise to the f
 unctional mature complex and 2) what are the accessory factors involved in
  the process. Thus\, the incorporation dynamics of the different structura
 l subunits and their presence in assembly intermediates have been studied 
 in control mouse tissue isolated mitochondria\, and also in cultured cells
  bearing mitochondrial DNA mutations that alter CIII assembly. Preliminary
  results suggest that the current yeast CIII assembly model would not exac
 tly fit how the process takes place in the mammalian organelles. On the ot
 her hand\, in the search for currently unknown CIII assembly factors\, the
  human protein LYRM7 was found to show high sequence homology to the recen
 tly identified yeast protein Mzm1. Studying the protein’s localization a
 nd function in human cells allowed to determine that this factor would als
 o work as a UQCRFS1 (Rieske Fe-S protein) chaperone. Our analyses showed t
 hat LYRM7/MZM1L binds to the catalytic subunit in a prior step to its tran
 slocation to the inner membrane and incorporation to CIII\, which is one o
 f the final steps in the enzyme’s maturation.
LOCATION:Sackler Lecture Theatre (Level 7) Wellcome Trust/MRC Building\, A
 ddenbrooke's Site
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