A new enzyme in cardiolipin synthesis

点击翻译按钮获取中文摘要

Cardiolipin is a special type of fat that makes up the inside lining of the mitochondria, which are considered the `powerhouses' of the cell. Cardiolipin is found in every organ, but there are different forms of cardiolipin in different organs. Because specific forms of cardiolipin are needed in different places, different organs have special little machines, called enzymes, that they use to convert cardiolipin from one form to another, and to make more when it is needed. This `remodeling' of cardiolipin is important for health. When the body doesn't make enough cardiolipin, or when the body doesn't make the right types of cardiolipin, diseases can result. In fact, changes in cardiolipin amount and type commonly occur in aging, and also in many different diseases, such as Alzheimer's and Parkinson's diseases, heart disease and stroke, cardiovascular disease, and diabetes. There are also genetic diseases, where children are born with a poor ability to remodel cardiolipin, and it can cause serious consequences like heart failure. We have discovered a new enzyme that remodels cardiolipin. We are very excited about this, since it is the first new discovery of its kind in almost 10 years. We are also excited because some of the previous discoveries have been by Canadians, which means that we can help to make Canada a global leader in this field. There is a lot of this enzyme in the brain, and also in the heart and muscle which are all very energetic tissues that need to make a lot of power. There is also some in the fat, which is exciting, because changes in energy production in fat can affect weight gain. To find out more about how this enzyme works, and what it does in the body, we are going to study it in cells, and also make it in an isolated, purified form. This lets us let test how well it works, what specific types of cardiolipin it makes, and how changing those forms changes how well cells can work to make energy. This will tells us a lot about this new enzyme, but also about how cells work. We are also going to study what it does in the body. Normally, humans and mice have two copies of DNA that contains the blueprint for making this enzyme. We have made special mice that are missing one of those copies. We are going to breed the mice together, so that we make mice that don't have any copies. We have a lot of experience testing mice for normal function, and for disease. We are going to study these special mice to see how much they are affected by losing this enzyme. We are going to study their brains, to see if they have memory problems, and problems with the cells and molecules that control learning. We will also study their muscle and fat, to see if it changes how well they work. This information will help us to understand how humans function, which is important for health and disease.