Mitochondrial biogenesis and human disease

Mitochondria have a central role in producing energy in a suitable form for biological processes. They are also involved in programmed cell death, and in maintaining appropriate levels of calcium in cells. These activities require mitochondria to communicate with the cellular nucleus, and one way that signalling is carried out involves very reactive oxygen molecules that are generated in mitochondrion. When these processes go wrong, they can lead to human diseases including heart disease, diabetes, neurodegenerative disorders, obesity and cancer. If we understand the basic processes, we are more likely to understand what is happening when these processes in the mitochondrion go wrong, and to be able to provide therapies to compensate for or correct the faults. This programme will study how the mitochondria themselves are made and put together, and how they increase their numbers in response to the changing requirements of the cell. It will try and to provide diagnostic tests and therapies for patients when these processes no longer work properly.|

The biogenesis of mitochondria is a complex process controlled by communication between the nucleus and the organelle. It requires the coordination of the cytoplasmic synthesis and import into the organelle of about 1,500 proteins encoded in the nucleus, with the synthesis in the organelle of 13 proteins encoded by mtDNA, followed by the assembly of multisubunit enzyme complexes containing proteins from both genomes. In addition, it involves the regulation of fission and fusion of mitochondria, and of the turnover of mitochondria by mitophagy in response to various stimuli. Disruption of any of these processes in human can lead to defective mitochondria and pathology. The aim of this programme is to identify the mechanisms involved in biogenesis of mitochondria especially those involving the mitochondrial inner membrane protein, MPV17.