Periodic Reporting for period 1 - RSC (Atomic Resolution Structures of Mitochondrial Respiratory Chain Supercomplexes)
Reporting period: 2016-09-01 to 2018-08-31
We are trying to understand the regulation and function of the mitochondrial electron transport chain, a series of large membrane protein complexes that are central to our metabolism. These complexes form into supercomplexes the function of which are unclear. We are solving the structures of these supercomplexes in order to get a better understanding of their role in metabolism. Defects of the mitochondrial electron transport chain cause severe neuro-degenerative diseases and high-resolution structures of the supercomplexes will help us to better understand the disease mechanisms and may lead to new therapies. The overall objectives of the project are to get high resolution structures of the mitochondrial electron transport chain complexes that will give us insight into the mechanism of the individual complexes and how they work together. We also hope to get insight into how malfunctioning of the complexes lead to disease.
Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far
The project has involved the development of methods for the purification and structure determination of respiratory supercomplexes and complex I of the mitochondrial electron transport chain. The work has resulted in the publication of two papers which have had a large impact on our understanding of these protein complexes that are central to our metabolism. A third paper is in the process of being put together and should be published in the fall.
Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far)
The structures reported in this publication were the highest resolution structures motichondrial electron transport chain at the time and remain state of the art for understanding supercomplex architecture and mechanism. Besides the significant contribution to our understanding of metabolism and a high impact publication in the journal Nature, there are no immediate socio-economic impacts. We continue to strive to improve the resolution of the supercomplex to give more insight into the fundamental mechanisms of our metabolism which should provide greater future impact. An additional publication is in preparation and will be submitted before the end of the project.