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Spatio-temporal assembly of respiratory chain complexes RCCs in mitochondrial fusion and fission dynamics

线粒体融合和裂变动力学中呼吸链复合物 RCC 的时空组装

基本信息

批准号：
41407014
负责人：
Professorin Dr. Karin Busch
金额：
--
依托单位：
Institut für Integrative Zellbiologie und Physiologie (IIZP)
依托单位国家：
德国
项目类别：
Research Grants
财政年份：
2007
资助国家：
德国
起止时间：
2006-12-31 至 2016-12-31
项目状态：
已结题

来源：
https://gepris.dfg.de/gepris/projekt/41407014?language=en
关键词：
Spatio temporal assembly respiratory chain

项目摘要

Mitochondria are the bioenergetic cell organelles of higher non-green eukaryotes. They provide the vast majority of ATP, the cellular energy currency. ATP is generated by the concerted action of five membrane protein complexes. It involves the step-wise oxidation of substrates in a redox-chain cou-pled to the generation of a proton gradient across the membrane, which provides the electrochemical energy for ATP synthesis is the last step. This beautiful realization of energy production bears several challenges, though, and is sensitive to perturbance. Distortion of the balanced reactions of the res-piratory chain has severe consequences not only for mitochondrial function but for the cellular fate in general. Mitochondrial impairment is closely associated with the development of neuro-degenerative diseases and plays an important role in the process of aging. To keep mitochondria in good perfor-mance, several quality control levels are established. Mitochondrial fusion and fission plays an im-portant role in this. Roughly, it enables the re-mixing of mitochondrial compounds and helps to sepa-rate dysfunctional mitochondria for further elimination by mitophagy. Importantly, the molecular mechanisms leading to the development of functional heterogeneity in different regions of a cell or within single mitochondria are poorly understood. The peculiar ultrastructure of mitochondria, the unu-sual organelle dynamics and the specific properties of the respiratory chain complexes which assem-bly in supercomplex structures show an integrate interplay that adds another level of complexity. Our contribution to this challenging area is the spatio-temporal dissection of the organization of the res-piratory chain. In our project we aim to understand the intimate relation between inner membrane archi-tecture, protein distribution and functional performance. We observed that owing to the structur-al/functional microcompartmentation, re-mixing of respiratory chain complexes during mitochondrial fusion and fission dynamics is limited and results in local heterogeneity. To unravel, how this evolves and what consequences it has for quality control and cellular health, we will dissect the organization of the respiratory chain under various conditions. By use of highly advanced live imaging techniques in combination with ample molecular biology we hope to gain a fundamental understanding how the mitochondrial bioenergetic system is spatio-temporally and functionally organized. In the context of mitochondrial failure in neuro-degenerative diseases this will provide new information how mitochon-drial quality control is contested and - maintained.

线粒体是高等非绿色真核生物的能量细胞器。它们提供了绝大多数的ATP，细胞能量货币。ATP是由五种膜蛋白复合物协同作用产生的。它涉及氧化还原链中底物的逐步氧化，并与跨膜质子梯度的产生相耦合，这为ATP合成提供了电化学能，是最后一步。然而，这种美丽的能源生产的实现面临着一些挑战，并且对扰动很敏感。呼吸链平衡反应的扭曲不仅对线粒体功能而且对细胞命运具有严重后果。线粒体损伤与神经退行性疾病的发生发展密切相关，在衰老过程中起重要作用。为了保持线粒体的良好性能，建立了几个质量控制水平。线粒体的融合和分裂在其中起着重要作用。粗略地说，它能够重新混合线粒体化合物，并有助于分离功能障碍的线粒体，以通过线粒体自噬进一步消除。重要的是，导致细胞不同区域或单个线粒体内功能异质性发展的分子机制知之甚少。线粒体的特殊超微结构、异常的细胞器动力学和组装成超复杂结构的呼吸链复合体的特殊性质显示出一种综合的相互作用，增加了另一个层次的复杂性。我们对这个具有挑战性的领域的贡献是呼吸链组织的时空解剖。本研究旨在了解细胞内膜结构、蛋白质分布和功能表现之间的密切关系。我们观察到，由于结构/功能微区室化，呼吸链复合物在线粒体融合和裂变动力学过程中的重新混合是有限的，并导致局部异质性。为了阐明这是如何演变的，以及它对质量控制和细胞健康有什么影响，我们将在各种条件下解剖呼吸链的组织。通过使用高度先进的实时成像技术，结合丰富的分子生物学，我们希望获得一个基本的了解如何线粒体生物能量系统的时空和功能组织。在神经退行性疾病中线粒体衰竭的背景下，这将提供如何竞争和维持线粒体质量控制的新信息。