Phosphatidylethanolamine deficiency in mammalian mitochondria

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The functioning of all mammalian cells requires energy, the majority of which is produced in mitochondria, the power stations of the cell. Like other membranes in the cell, mitochondria contain lipids and proteins that form the barriers that restrict the movement of molecules within cells, and in and out of cells. The major lipids in animal cells are cholesterol and phospholipids. Two important phospholipids are phosphatidylserine (PS) and phosphatidylethanolamine (PE). These lipids are interconvertible and contribute to the structure and integrity of membranes, as well as to the functioning of proteins embedded in the membranes. Alteration of the lipid composition of mitochondria can have profound consequences for mitochondrial function and energy production. PE is enriched in mitochondrial membranes compared to other membranes of the cell. We have shown that mice that are unable to make PE in mitochondria have aberrant mitochondria and do not survive during development. Therefore, the overall goal of my lab is to test the hypothesis that reduction of the PE content of mitochondria alters the structure of these organelles and impairs mitochondrial function and energy production. For these studies, we shall use genetically-altered cultured cells in which the production of PE and/or its precursor, PS, has been markedly reduced. We shall determine the minimum amount of mitochondrial PE that is required for specific functions of mitochondria, such as energy production. Subsequently, we shall determine if reduction in PE content of mitochondria specifically in the heart of mice, a mitochondria-rich tissue, impairs heart function. We anticipate that these fundamental studies on the function of membrane phospholipids will reveal new roles for these molecules in mammalian cells and animals.