Physio-pathology of mitochondrial complex III assembly

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• Dr Erika Fernandez-Vizarra
• Wednesday 17 October 2012, 15:00-16:00
• Sackler Lecture Theatre (Level 7) Wellcome Trust/MRC Building, Addenbrooke's Site.

If you have a question about this talk, please contact Penny Peck.

Despite its central role in oxidative phosphorylation and other metabolic pathways, there are many aspects of mammalian mitochondrial Complex III (CIII) biogenesis that are still unknown. Most of the current knowledge about how CIII is assembled has been obtained by studying the yeast S. cerevisiae, which is a good model due to the enzyme’s conserved structure. However, there are important differences between yeast and mammals concerning mitochondrial biogenesis, which underscore the necessity to study the process in mammalian mitochondria to properly understand it. Two main aspects of CIII assembly have been analyzed by using human and mouse systems: 1) how the subunits are brought together to give rise to the functional mature complex and 2) what are the accessory factors involved in the process. Thus, the incorporation dynamics of the different structural 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 exactly fit how the process takes place in the mammalian organelles. On the other hand, in the search for currently unknown CIII assembly factors, the human protein LYRM7 was found to show high sequence homology to the recently identified yeast protein Mzm1. Studying the protein’s localization and function in human cells allowed to determine that this factor would also work as a UQCRFS1 (Rieske Fe-S protein) chaperone. Our analyses showed that LYRM7 /MZM1L binds to the catalytic subunit in a prior step to its translocation to the inner membrane and incorporation to CIII , which is one of the final steps in the enzyme’s maturation.

This talk is part of the MRC Mitochondrial Biology Unit Seminars series.

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• Life Science Interface Seminars
• MRC Mitochondrial Biology Unit Seminars
• Sackler Lecture Theatre (Level 7) Wellcome Trust/MRC Building, Addenbrooke's Site
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