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Post-translational control of mitochondria by the ubiquitin ligase Fbxo7

Supervisor: Dr Heike Laman

Based at the Department of Pathology, Tennis Court Road

Mitochondria are integral to multiple essential cellular activities including energy production, metabolism and cell death.  Different cell types have requirements of mitochondria.  Some cells have a high demand for energy production, like cardiac muscle and neurons, while others shed or remodel mitochondria as part of their development, like erythrocytes and sperm. Sometimes, mitochondria are transiently used in specialized, functional structures, such as the immune synapses in T lymphocytes.  Thus the proper control of the mitochondrial network, including its biogenesis and energy production to its dynamics and the disposal of damaged portions via mitophagy, is central to a healthy lifespan. The E3 ubiquitin ligase adaptor protein Fbxo7 has been shown to act as part of the stress-induced PINK1/Parkin mitophagy pathway, and it also regulates basal mitochondrial function. The student will take a biochemical approach to investigate the regulatory mechanisms Fbxo7 utilises to regulate mitochondria under developmental, adaptive and stress-induced conditions. 

Recent Publications

- F. R. Teixeira*, S. J. Randle*, S. P. Patel*, T. E. T. Mevissen, G. Zenkeviciute, Tie Koide, D. Komander, H. Laman. 2016. Gsk3β and Tomm20 are substrates of the SCF(Fbxo7/PARK15) ubiquitin ligase associated with Parkinson's disease. Biochem J.  15;473(20):3563-3580. PMID: 27503909

- V. Burchell*, D. Nelson*, A. Sanchez-Martinez*, M. Delgado-Camprubi, R. Ivatt, J. Pogson, S. J. Randle, S. Wray, P. A. Lewis, H. Houlden, A. Abramov, J. Hardy, N. Wood, A. J. Whitworth, H. Laman and H. Plun-Favreau. 2013. The Parkinson’s disease genes Fbxo7 and parkin interact to mediate mitophagy. Nat Neurosci. 2013 Aug 11. doi: 10.1038/nn.3489. PMID:23933751

- D. E. Nelson, S. J. Randle and H. Laman. 2013.  Beyond ubiquitination:  The atypical functions of Fbxo7 and other F-box proteins.  Open Biol. 2013 Oct 9;3(10):130131. doi: 10.1098/rsob.130131. PMID:24107298