REGULATION OF ER-MITOCHONDRIA CONTACTS IN NEURODEGENERATION

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In the brain, approximately 100 billion nerve cells allow us to think, remember, see, hear, speak etc. Inside of the nerve cells there are different compartments, called organelles. We call them organelles because for a cell they are more or less what an organ such as the liver is for the whole body. Organelles are surrounded by membranes; you can compare them to little balloons. Just as organs, organelles have specific functions. We are particularly interested in two of these organelles, called mitochondria and ER (ER is short for Endoplasmic Reticulum). Mitochondria are the organelles that convert the food we eat into a form of energy that the cells can use. They basically are the power stations of the body. The ER is the place in the cell where various building blocks of the cell, called proteins and lipids are made and then sent to specific places in the cell. Mitochondria and ER can swap energy and building blocks between them at places where the organelles touch. We call these places contact sites. It has become clear that when contact sites between ER and mitochondria are disrupted that this contributes to brain diseases such as motor neuron disease, dementia and Parkinson's disease. We don't know why this is so.We have discovered a new mechanism that controls the amount of contact there is between the ER and mitochondria, and we believe that overactivation of this mechanism might be the reason that there is loss of contact in disease.The purpose of this project is to investigate this new mechanism so that we can better understand what is going on. Once we know this we will try to use this knowledge to find new ways of restoring the contacts between the organelles. Once we can restore the contacts we can answer the question if this protects neurones in a dish from dying. Our hope is that this will be the case and that we can use what we learn in this project as the starting point to develop new drugs to treat brain diseases.