COMPIB · Characterisation of mitochondrial proteins in brain

Final Activity Report Summary - COMPIB (Characterisation of Mitochondrial Proteins in Brain)

Mitochondria are cellular organelles play an essential role in controlling energy flow in the brain. Through the process of oxidative phosphorylation they deliver the majority of adenosine triphosphate (ATP), a molecule that that ensures normal brain function. However, mitochondria are not perfect and under certain conditions may be detrimental to the brain as they may produce excessive production of reactive oxygen species. These reactive oxygen species or free radicals may be very damaging to brain tissue and are thought to be part of the normal aging process in the brain. In addition, under certain conditions, mitochondria control the process of neurodegeneration in the brain by releasing signals that signal and control mechanisms of programmed cell death. A large collection of proteins in mitochondria contribute to the normal/abnormal functioning of these organelles which in turn has important implications for a number of human diseases such as age-related diseases such as Parkinson's disease and Alzheimer's disease. A number of functional differences are known to be present in mitochondria from different organ/tissue sources, however, until now no one has performed a comprehensive analysis of all the proteins (proteome) present in different types of brain mitochondria. In the Department of Biochemistry, Trinity College Dublin, there are a collection of mitochondrial and neurodegenerative researchers as well as proteomics and imaging facilities. However, experienced researchers with expertise in all of these areas were lacking, therefore, the Marie Curie TOK program funded a proposal to transfer knowledge from experts in the proteomics and imaging field to experts in the mitochondria field in Trinity College Dublin. In return, the Marie Curie Research fellows received intensive training in the area of bioenergetics and neurodegenerative diseases. The outcome of the project has been extremely successful in that a centre for research on mitochondrial function/dysfunction has been established at Trinity College Dublin and important knowledge has been transferred from centres of excellence in Europe to research scientists. This activity has generated European scientists with increased knowledge on new bioanalytical techniques as well as producing fundamental knowledge on the nature of mitochondria in the brain. The COMPIB team made major discoveries by showing that the mitochondria proteins present in one of the most important regions of the brain, the nerve terminal, are different by up to 30 % in comparison to mitochondrial from other parts of the brain. Research carried out during the COMPIB project showed that some of these proteins are vital for controlling movement of mitochondria to the nerve terminal as well as for production of ATP in this region. Major differences in the mitochondrial respirasome were identified and research into the ramifications of such structural differences is continuing. Concerning the proteins that we found specific to synaptic mitochondria, the COMPIB team established a series of new imaging techniques to observe the importance of such proteins in controlling trafficking of mitochondria in the neuron as well as important fusion/fission events. This research is continuing and the transfer of knowledge on proteomics and imaging techniques from EMBL, Dunn Institute, University of Siena and Kadir Has University to Trinity has ensured that further discovery will be made in the brain mitochondria area.

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