Characterization of lipid metabolic machines within mitochondria

线粒体内脂质代谢机器的表征

• 批准号: RGPIN-2015-05969
• 负责人: McQuibban, George
• 金额: $ 2.19万
• 依托单位: University of Toronto
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2017
• 资助国家: 加拿大
• 起止时间: 2017-01-01 至 2018-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=629274
• 关键词: Characterization; lipid; metabolic; machines; within

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.

线粒体是细胞的发电站。它们的功能取决于一个非常精确的结构，由4个生物化学上不同的隔室定义。从外到内，这些隔室是：1）外膜，2）膜间空间，3）内膜，和4）基质。越来越明显的是，存在几种优雅的机制来保持这一重要细胞器的保真度。我的实验室长期以来一直对理解线粒体动力学、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都很重要。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感兴趣。我们的假设是，内膜中的脂质代谢是由非常精确的机制精心组织成集中在内膜褶皱处称为嵴的子域。事实上，我们有初步的证据表明，心磷脂（CL）和磷脂酰丝氨酸（PS）的代谢是协调的大酶复合物，这些代谢酶改变线粒体生物学。