'Disulfide bond formation in biogenesis of mitochondrial proteins'

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• Professor Agnieszka Chacinska, International Institute of Molecular and Cell Biology, Poland
• Wednesday 15 December 2010, 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.

Mitochondria play a critical role in cellular metabolism and have also been strongly implicated in apoptosis, ageing and a number of diseases. Biogenesis of mitochondrial proteins is a multi-step process that, beside synthesis, involves their subsequent transport, folding into their 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 previously described in mitochondria. The MIA pathway represents a novel disulfide-transferring system to control the vectorial translocation of proteins into mitochondria. Mia40, one of the essential components of this pathway, acts in a receptor-like manner. It shows a striking selectivity in the protein substrate recognition, thereby dictating substrate entry to the MIA pathway. This mode of action stands in contrast to mechanisms utilized by other, rather promiscuous, disulfide transferring enzymes such as DsbA and PDI . Furthermore, a mode of the cooperation between Mia40 and the sulfhydryl oxidase Erv1 is unique. We propose that the simultaneous association of Mia40, Erv1 and a substrate protein in the ternary complex allows the efficient transfer of multiple disulfide bonds into substrate proteins. 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 functioning.

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

This talk is included in these lists:

• All Talks (aka the CURE list)
• CamBridgeSens
• Cambridge talks
• Life Science Interface Seminars
• MRC Mitochondrial Biology Unit Seminars
• Sackler Lecture Theatre (Level 7), Wellcome Trust/MRC Building, Addenbrooke's Site
• Trust & Technology Initiative - interesting events

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