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Understanding the novel oxidative folding and complex assembly mechanisms of mitochondrial Tim9/Tim10
Reference
BB/C514323/1
Principal Investigator / Supervisor
Dr Hui Lu
Co-Investigators /
Co-Supervisors
Institution
The University of Manchester
Department
Life Sciences
Funding type
Research
Value (£)
256,155
Status
Completed
Type
Research Grant
Start date
31/08/2005
End date
30/11/2008
Duration
39 months
Abstract
Protein import is essential for the biogenesis of mitochondria. More than 95 per cent of the mitochondrial proteins are encoded by nuclear genes and synthesised in the cytosol as precursors. Then proteins must be imported into and folded in specific compartments of the organelle. A central facet of this import process is the Tim9-Tim10 complex, which facilitates the transport of hydrophobic inner membrane proteins across the aqueous intermembrane space (IMS). Formation of the Tim9-Tim10 complex relies on correct oxidative folding of its components Tim9 and Tim10. Both proteins are individually imported into mitochondria in a Cys-reduced state, and then oxidatively folded into an assembly-competent state to form the Tim9-Tim10 complex. At present, the oxidative folding pathway followed by these proteins and the process by which the complex assembles are unknown. Furthermore, the mechanism by which protein disulphide bonds are efficiently formed within mitochondria is also completely uncharacterised. The aims of this project are to exploit recent advances in our understanding of the import and function of yeast mitochondrial proteins to study (1) the novel oxidative folding pathway of mitochondrial Tim9 and Tim10, (2) the detailed assembly mechanism of the Tim9-Tim10 complex, and (3) the factors regulating the redox conditions within the mitochondrial IMS.
Summary
unavailable
Committee
Closed Committee - Biomolecular Sciences (BMS)
Research Topics
Structural Biology
Research Priority
X – Research Priority information not available
Research Initiative
X - not in an Initiative
Funding Scheme
X – not Funded via a specific Funding Scheme
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