Novel Roles for COX Assembly Factors in Mitochondrial Homeostasis

COX 组装因子在线粒体稳态中的新作用

• 批准号: RGPIN-2017-04216
• 负责人: Glerum, DMoira
• 金额: $ 1.89万
• 依托单位: University of Waterloo
• 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=629281
• 关键词: Novel; Roles; COX; Assembly; Factors

Mitochondria are sub-cellular compartments responsible for producing the bulk of the energy our cells need for survival. In addition to their central role in energy production, mitochondria are crucial for programmed cell death, an important component of the life-death balance for every living cell. My lab is focusing on cytochrome oxidase (COX), the terminal electron acceptor of the mitochondrial respiratory chain, the energy-producing machinery. In addition to its protein subunits, COX also requires a host of accessory proteins that provide copper and heme A for enzyme assembly. In the most recent granting period, we have found that Cox17 is more abundant in wild-type stationary phase yeast and that loss of Cox17 results in an inability to induce apoptosis in stationary phase yeast, suggesting for the first time that this small protein, better known as a mitochondrial copper chaperone, may also have role in cellular quality control. In addition, we have found that a lack of assembled COX also leads to an increase in oxidative stress.

线粒体是亚细胞隔间，负责产生我们细胞生存所需的大部分能量。除了在能量生产中的核心作用外，线粒体对细胞程序性死亡至关重要，程序性细胞死亡是每个活细胞生死平衡的重要组成部分。我的实验室专注于细胞色素氧化酶(COX)，这是线粒体呼吸链的末端电子受体，是产生能量的机械。除了它的蛋白质亚基，COX还需要大量的辅助蛋白质，为酶的组装提供铜和血红素A。在最近的授权期，我们发现Cox17在野生型固定相酵母中含量更高，并且Cox17的缺失导致无法在固定相酵母中诱导细胞凋亡，这首次表明这种更为人所知的线粒体铜伴侣蛋白也可能在细胞质量控制中发挥作用。此外，我们还发现，缺乏组装的COX也会导致氧化应激增加。