Investigation of the function of the ER/mitochondria contact sites in cell physiology and disease

内质网/线粒体接触位点在细胞生理学和疾病中的功能研究

• 批准号: MC_UU_00015/7
• 负责人: Julien Prudent
• 金额: $ 191.77万
• 依托单位: University of Cambridge
• 依托单位国家: 英国
• 项目类别: Intramural
• 财政年份: 2017
• 资助国家: 英国
• 起止时间: 2017 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=MC_UU_00015%2F7
• 关键词: Investigation; function; ER; mitochondria; contact

Mitochondria are highly dynamic organelles essential for the survival of the cell. Mitochondrial dynamics has been linked to different physiological functions, and contacts with other organelles are required for specific metabolic activity and mitochondrial behaviour. Indeed, endoplasmic reticulum and mitochondria work together and their closed juxtaposition is considered as a signalling platform for metabolite flux. Alteration of these contacts has been associated with defects in cellular homeostasis and with human disease. The goal of our group is to characterise the architecture and understand the associated functions of these inter-organelle contacts. Using biochemical, molecular and cell biological approaches, we want to investigate the function of the mitochondria/endoplasmic reticulum contact sites in different cell physiology processes including cell death, lipid and calcium fluxes and cell migration. This work will lead us to obtaining new insights into the importance of mitochondria and mitochondria/ER contacts in cellular signalling pathways, and to better understanding the pathomechanisms underpinning human diseases associated with defects in their regulation and dynamics.

线粒体是高度动态的细胞器，对细胞的生存至关重要。线粒体动力学与不同的生理功能有关，与其他细胞器的接触是特定的代谢活动和线粒体行为所必需的。事实上，内质网和线粒体一起工作，它们的紧密并列被认为是代谢产物流动的信号平台。这些接触的改变与细胞内稳态的缺陷和人类疾病有关。我们小组的目标是描述这些细胞器间联系的结构特征和相关功能。我们希望通过生物化学、分子生物学和细胞生物学的方法，研究线粒体/内质网接触部位在不同的细胞生理过程中的功能，包括细胞死亡、脂质和钙的流动以及细胞的迁移。这项工作将使我们对线粒体和线粒体/内质网接触在细胞信号通路中的重要性获得新的见解，并更好地理解与它们的调节和动力学缺陷相关的支持人类疾病的病理机制。

项目成果

Cryo-EM structures of mitochondrial respiratory complex I from Drosophila melanogaster.

• DOI: 10.7554/elife.84424
• 发表时间: 2023-01-09
• 期刊: ELIFE
• 影响因子: 7.7
• 作者: Agip, Ahmed-Noor A.;Chung, Injae;Sanchez-Martinez, Alvaro;Whitworth, Alexander J.;Hirst, Judy
• 通讯作者: Hirst, Judy

Cryo-EM structures of complex I from mouse heart mitochondria in two biochemically defined states.

来自小鼠心脏线粒体的复合物 I 的冷冻电镜结构处于两种生化定义的状态。

• DOI: 10.17863/cam.26226
• 发表时间: 2018
• 作者: Agip A

A two-nuclease pathway involving RNase H1 is required for primer removal at human mitochondrial OriL.

• DOI: 10.1093/nar/gky708
• 发表时间: 2018-10-12
• 期刊: Nucleic acids research
• 影响因子: 14.9
• 作者: Al-Behadili A;Uhler JP;Berglund AK;Peter B;Doimo M;Reyes A;Wanrooij S;Zeviani M;Falkenberg M
• 通讯作者: Falkenberg M

An assessment of the rescue action of resveratrol in parkin loss of function-induced oxidative stress in Drosophila melanogaster.

白藜芦醇对黑腹果蝇帕金功能丧失诱导的氧化应激的救援作用评估。

• DOI: 10.17863/cam.82284
• 发表时间: 2022
• 作者: Adedara A