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Understanding the functional mechanism of mitochondrial AAA proteases in protein quality control

Project Description

Maintenance of proper protein homeostasis is essential for cell viability and growth. Defects in protein quality control and the accumulation of damaged proteins is widely accepted as a cause or factor in many diseases (e.g. cancer, diabetes, various neurodegenerative diseases) and ageing. Mitochondrial AAA proteases play multifunctional roles that are not only important in mitochondrial function per se, but also in protein quality control of both mitochondrial and non-mitochondrial proteins. The overall aim of this proposed project is to understand the functions the mitochondrial AAA proteases, and molecular mechanisms of the proteases. A wide range of methods, from proteomic, yeast cell biology to biochemical and biophysical techniques, will be used to address the function and functional mechanisms of the mitochondrial AAA proteases. Candidates are expected to hold (or be about to obtain) a minimum upper second class honor’s degree (or equivalent) in biochemistry, cell biology or a related subject.

Funding Notes

This project has a Band 2 fee. Details of our different fee bands can be found on our website (View Website). For information on how to apply for this project, please visit the Faculty of Biology, Medicine and Health Doctoral Academy website (View Website).

Informal enquiries may be made directly to the primary supervisor.


• Martinelli P, Rugarli EI. Emerging roles of mitochondrial proteases in neurodegeneration. Biochim Biophys Acta. 2010 1797:1-10
• Voos W, Jaworek W, Wilkening A, Bruderek M. Protein quality control at the mitochondrion. Essays Biochem. 2016 Oct 15;60(2):213-225. Review
• Spiller MP, Guo L, Wang Q, Tran P, Lu H. Mitochondrial Tim9 protects Tim10 from degradation by the protease Yme1. Biosci Rep. 2015 Mar 17;35(3). pii:e00193.
• Schreiner B, Westerburg H, Forné I, Imhof A, Neupert W, Mokranjac D. Role of the AAA protease Yme1 in folding of proteins in the intermembrane space of mitochondria. Mol Biol Cell. 2012 22:4335-46.

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