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

线粒体和内质网(ER)形成紧密的接触部位，与多种细胞功能(如钙缓冲、脂质运输、线粒体形态)有关，它们的破坏与神经退行性疾病有关。目前尚不清楚这些接触部位是如何组装和调节的，以及内质网-线粒体接触的中断如何影响细胞的其余部分，特别是细胞信号。该项目将(1)表征一种新的完整线粒体蛋白与内质网驻留蛋白的相互作用，(2)研究线粒体故障如何影响培养细胞和原代皮质神经元内质网-线粒体接触的稳定性和形成，以及扰动对内质网-线粒体接触的信号后果是什么。

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.