Characterization of lipid metabolic machines within mitochondria

线粒体是细胞的动力源。它们的功能依赖于一个非常精确的结构，由4个生物化学上不同的隔间定义。从外到内，这些隔室分别是：1)外膜，2)膜间空间，3)内膜，4)基质。越来越明显的是，存在一些优雅的机制来维持这一基本细胞器的保真度。我的实验室长期以来一直对了解线粒体动力学，正在进行的膜融合和裂变反应感兴趣，这对许多细胞生物学结果很重要。最近，我们对线粒体内膜的基本结构以及它如何与内外膜之间的脂质动力学相关产生了兴趣。我们的假设是，细胞膜中的脂质代谢是由非常精确的机器精心组织的，这些机器被精心组织成集中在称为嵴的细胞膜折叠处的子域。事实上，我们有初步证据表明，心磷脂（CL）和磷脂酰丝氨酸（PS）的代谢是由大型酶复合物协调的，这些代谢酶改变线粒体生物学。

Mitochondria are the powerhouse of the cell. Their functionality depends on a very precise architecture that is defined by 4 biochemically distinct compartments. From outside to in, these compartments are: 1) the outer membrane, 2) the inter-membrane space, 3) the inner membrane, and 4) the matrix. It is becoming increasingly evident that several elegant mechanisms exist to maintain the fidelity of this essential organelle. My lab has had a long-standing interest in understanding mitochondrial dynamics, the ongoing membrane fusion and fission reactions, that are important for many cell biological outcomes. More recently, we have become interested in the basic architecture of the mitochondrial inner membrane, and how it may be related to lipid-dynamics between the inner and outer membranes. It is our hypothesis that lipid metabolism in the inner membrane is orchestrated by very precise machineries that are carefully organized into sub-domains concentrated at the inner membrane folds called cristae. Indeed, we have initial evidence that shows cardiolipin (CL) and phosphatidylserine (PS) metabolism is co-ordinated by large enzyme complexes and that these metabolic enzymes alter mitochondrial biology. We propose to: 1) Understand how lipid metabolism is linked to mitochondrial morphology; 2) Identify and characterize the components of the lipid metabolic complex; and 3) Characterize the function of the lipid metabolic complex in mitochondrial quality control. This NSERC-funded program will provide the framework to train several HQP, most notably, two PDFs, two graduate students, and several undergraduate students including one summer student (each summer) and at least one undergraduate per university annual semester (10 minimum in total) for the duration of the funding period.