Role of prohibitins for proteolytic processes within mitochondria

抑制素对线粒体内蛋白水解过程的作用

• 批准号: 5422907
• 负责人: Professor Dr. Thomas Langer
• 金额: --
• 依托单位: Max-Planck-Institut für Biologie des Alterns
• 依托单位国家: 德国
• 项目类别: Priority Programmes
• 财政年份: 2004
• 资助国家: 德国
• 起止时间: 2003-12-31 至 2008-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/5422907?language=en
• 关键词: Role; prohibitins; proteolytic; processes; within

Prohibitins comprise a conserved and ubiquitous family of eukaryotic proteins which exhibit sequence similarity to eubacterial HflK and HflC, regulatory proteins of the AAA protease FtsH. Prohibitins are localised to the mitochondrial inner membrane where they form a high molecular mass complex and assemble with the m-AAA protease. We observed an accelerated degradation of inner membrane proteins by the m-AAA protease in yeast mitochondria lacking prohibitins pointing to a regulation of AAA proteases which is conserved from eubacteria to eukaryotes. In the proposed research project, we will characterise the regulatory role of prohibitins during membrane protein degradation. It will be of particular interest to examine whether the prohibitin complex exerts chaperone activity during proteolysis and/or affects the enzymatic activity of the m-AAA protease. We will furthermore characterise the biogenesis of the prohibitin complex and analyse the structural organisation of purified complexes by electron microscopy. Genetic synthetic lethal and suppressor screens aim at the identification of functional interaction partners of prohibitins in mitochondria. These studies should also reveal a potential link between the turnover of mitochondrial inner membrane proteins and diverse cellular functions previously attributed to prohibitins including senescence, cell cycle regulation and cancer, and the maintenance of mitochondrial morphology

禁止蛋白包括一个保守且普遍存在的真核蛋白家族，其序列与真细菌HflK和HflC （AAA蛋白酶FtsH的调节蛋白）相似。禁止蛋白定位于线粒体内膜，在那里它们形成一个高分子量复合物并与m-AAA蛋白酶组装。我们在酵母线粒体中观察到缺乏禁止素的m-AAA蛋白酶对内膜蛋白的加速降解，这表明AAA蛋白酶的调控从真细菌到真核生物都是保守的。在拟议的研究项目中，我们将描述禁止蛋白在膜蛋白降解过程中的调节作用。研究禁止蛋白复合物是否在蛋白水解过程中发挥伴侣活性和/或影响m-AAA蛋白酶的酶活性将是特别有趣的。我们将进一步描述禁止复合物的生物起源，并通过电子显微镜分析纯化复合物的结构组织。遗传合成致死和抑制筛选旨在鉴定线粒体中禁止蛋白的功能相互作用伙伴。这些研究还应该揭示线粒体内膜蛋白的转换与多种细胞功能之间的潜在联系，这些功能先前归因于禁止包括衰老，细胞周期调节和癌症，以及线粒体形态的维持