Role and mechanism of mitochondrial transport proteins (On the University’s application portal, please select "PhD in Medical Science at the MRC Mitochondrial Biology Unit").

Mitochondria are central to the utilization of sugars and fat by the eukaryotic cell in order to synthesise ATP via oxidative phosphorylation. They are also involved in the metabolism of amino acids, the synthesis of iron-sulphur clusters and haem, the generation of heat, and the replication, transcription and translation of mitochondrial DNA. In order to carry out these and other processes, small molecules have to be continuously exchanged between the cytosol and the mitochondrial matrix across the inner mitochondrial membrane to link the biochemical pathways. Members of the mitochondrial carrier family carry out a large number of these transport steps and have been associated with many serious diseases [1]. In addition, there are other transporters active, such as the mitochondrial pyruvate carrier [2]. There are large number of compounds that need to pass this membrane, but the identity of the transport proteins involved in their translocation is unknown. This project deals with the identification of uncharacterised transport proteins in mitochondria to establish their role in physiology and disease. We are also interested to characterise their transport mechanisms structurally [3].

References
[1] E.R.S. Kunji, M.S. King, J.J. Ruprecht, C. Thangaratnarajah, The SLC25 carrier family: important transport proteins in mitochondrial physiology and pathology, Physiology, 35 (2020) 302-327.
[2] S. Herzig, E. Raemy, S. Montessuit, J.L. Veuthey, N. Zamboni, B. Westermann, E.R.S. Kunji, J.C. Martinou, Identification and functional expression of the mitochondrial pyruvate carrier, Science, 337 (2012) 93-96.
[3] J.J. Ruprecht, M.S. King, T. Zogg, A.A. Aleksandrova, E. Pardon, P.G. Crichton, J. Steyaert, E.R.S. Kunji, The molecular mechanism of transport by the mitochondrial ADP/ATP carrier, Cell, 176 (2019) 435–447.