Phosphatidylethanolamine deficiency in mammalian mitochondria

所有哺乳动物细胞的功能都需要能量，其中大部分能量是在细胞的发电站——线粒体中产生的。像细胞中的其他膜一样，线粒体含有脂质和蛋白质，它们形成屏障，限制分子在细胞内和进出细胞的运动。动物细胞中的主要脂质是胆固醇和磷脂。两种重要的磷脂是磷脂酰丝氨酸（PS）和磷脂酰乙醇胺（PE）。这些脂质是可相互转换的，有助于膜的结构和完整性，以及嵌入膜中的蛋白质的功能。线粒体脂质组成的改变对线粒体功能和能量产生有深远的影响。与细胞的其他膜相比，PE在线粒体膜中富集。我们已经证明，不能在线粒体中制造PE的小鼠具有异常的线粒体，并且不能在发育过程中存活。因此，我的实验室的总体目标是验证线粒体PE含量的降低会改变这些细胞器的结构并损害线粒体功能和能量产生的假设。对于这些研究，我们将使用转基因培养细胞，其中PE和/或其前体PS的产生已显着减少。我们将确定线粒体特定功能（如能量产生）所需的最小线粒体PE量。随后，我们将确定线粒体PE含量的减少是否会损害心脏功能，特别是在富含线粒体的小鼠心脏组织中。我们期望这些关于膜磷脂功能的基础研究将揭示这些分子在哺乳动物细胞和动物中的新作用。

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.