Elucidating the functions and interactions of mitochondrial porin in Neurospora

阐明脉孢菌线粒体孔蛋白的功能和相互作用

• 批准号: 184227-2011
• 负责人: Court, Deborah
• 金额: $ 2.19万
• 依托单位: University of Manitoba
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2011
• 资助国家: 加拿大
• 起止时间: 2011-01-01 至 2012-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=476523
• 关键词: Elucidating; functions; interactions; mitochondrial; porin

Eukaryotic cells contain membrane-bound compartments in which specialized functions occur. Mitochondria house much of the energy-generating machinery in the cell, using substrates produced outside of the organelle, and transporting products back into the cytoplasm. Mitochondria are bound by two membranes, and small molecules pass through the outer membrane via mitochondrial porin, also known as the voltage-dependent anion-selective channel (VDAC). This protein interacts with numerous proteins in and surrounding the mitochondria; these interactions are proposed to regulate basic metabolism, and in higher organisms, the initiation of apoptosis, or programmed cell death. To understand the function of porin, we are using Neurospora as a model organism; it contains a single porin gene, unlike humans which have three, including one essential form. A strain of Neurospora lacking porin has been generated, and suffers from deficiencies in energy-generating components (cytochromes), grows slowly and is cold-sensitive. Its mitochondria have altered structures and protein composition. The proposed work involves further characterizing these changes, and determining the complex set of factors that require porin for normal function. Genetic systems will be developed to express porin variants with defined sequence changes; the effects of these changes on the cells will enable determination of the different functional parts of porin.

真核细胞包含有特殊功能发生的膜结合的隔室。线粒体容纳了细胞内大部分的能量产生机制，利用细胞器外产生的底物，并将产物运送回细胞质。线粒体由两层膜结合，小分子通过线粒体孔蛋白穿过外膜，也称为电压依赖性阴离子选择通道（VDAC）。这种蛋白质与线粒体内和线粒体周围的许多蛋白质相互作用；这些相互作用被认为可以调节基本代谢，并在高等生物中调节细胞凋亡或程序性细胞死亡。为了了解孔蛋白的功能，我们使用神经孢子虫作为模式生物；它包含一个单一的孔蛋白基因，不像人类有三个，包括一个基本形式。已经产生了一种缺乏孔蛋白的神经孢子菌菌株，它缺乏能量产生成分（细胞色素），生长缓慢，对冷敏感。它的线粒体已经改变了结构和蛋白质组成。建议的工作包括进一步表征这些变化，并确定需要孔蛋白正常功能的复杂因素集。将开发遗传系统来表达具有确定序列变化的孔蛋白变体；这些变化对细胞的影响将有助于确定孔蛋白的不同功能部分。