Functional analysis of the human mitochondrial proteome
While we understand many aspects of mitochondrial function, we still do not fully appreciate the roles played by many individual proteins present in the organelle. Of the ~1300 proteins in human mitochondria, about 30% have no known function while another 30% have been assigned functions based on sequence similarity. We are coupling gene-editing techniques (TALENs and CRISPRs) to generate gene knockouts in cultured human cells and investigating how a protein's loss impacts mitochondria and the cell. This work is being coupled with state-of-the-art proteomic and bioinformatic approaches to determine how the cell changes its protein make-up to adjust to these changes. In our approach to functionalise the human mitochondrial proteome we are making new and important discoveries into fundamental aspects related to mitochondrial protein function.
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Stroud DA, Formosa LE, Wijeyeratne XW, Nguyen TN, Ryan MT. Gene knockout using transcription activator-like effector nucleases (TALENs) reveals that human NDUFA9 protein is essential for stabilizing the junction between membrane and matrix arms of complex I. J Biol Chem. 2013288(3):1685-90 Pubmed