Characterization of mitochondria-ER contact sites and their role in cellular signalling (P02)

线粒体-ER 接触位点的表征及其在细胞信号传导中的作用 (P02)

• 批准号: 290025802
• 金额: --
• 依托单位: Institut für Zellbiochemie
• 依托单位国家: 德国
• 项目类别: Collaborative Research Centres
• 财政年份: 2016
• 资助国家: 德国
• 起止时间: 2015-12-31 至 2018-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/290025802?language=en
• 关键词: Characterization; mitochondria; ER; contact; sites

Mitochondria and the endoplasmic reticulum (ER) form close appositions designated as contact sites which are implicated in several cellular functions (e.g. calcium buffering, lipid trafficking, mitochondrial morphology), and their disruption has been associated with neurodegenerative diseases. It remains unclear how these contact sites are assembled and regulated, and how the disruption of ER-mitochondria contacts affects the rest of the cell, in particular cellular signalling. This project will (1) characterize a novel interaction of an integral mitochondrial protein to an ER-resident protein and (2) study how mitochondrial malfunction affects the stability and formation of ER-mitochondria contacts in cultured cells and primary cortical neurons and what are the signalling consequences of perturbation on ER-mitochondria contacts.

线粒体和内质网（ER）形成紧密的并置，被指定为接触位点，其涉及几种细胞功能（例如钙缓冲、脂质运输、线粒体形态），并且它们的破坏与神经退行性疾病相关。目前尚不清楚这些接触位点是如何组装和调节的，以及ER-线粒体接触的破坏如何影响细胞的其余部分，特别是细胞信号传导。该项目将（1）表征一种完整的线粒体蛋白与ER驻留蛋白的新型相互作用，（2）研究线粒体功能障碍如何影响培养细胞和原代皮层神经元中ER-线粒体接触的稳定性和形成，以及ER-线粒体接触扰动的信号传导后果。