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PDZD8-FKBP8 tethering complex at ER-mitochondria contact sites regulates mitochondrial complexity. ER-线粒体接触点上的 PDZD8-FKBP8 拴系复合物调节线粒体的复杂性。
Pub Date : 2024-06-03 DOI: 10.1101/2023.08.22.554218
Koki Nakamura, Saeko Aoyama-Ishiwatari, Takahiro Nagao, Mohammadreza Paaran, Christopher J Obara, Yui Sakurai-Saito, Jake Johnston, Yudan Du, Shogo Suga, Masafumi Tsuboi, Makoto Nakakido, Kouhei Tsumoto, Yusuke Kishi, Yukiko Gotoh, Chulhwan Kwak, Hyun-Woo Rhee, Jeong Kon Seo, Hidetaka Kosako, Clint Potter, Bridget Carragher, Jennifer Lippincott-Schwartz, Franck Polleux, Yusuke Hirabayashi

Mitochondria-ER membrane contact sites (MERCS) represent a fundamental ultrastructural feature underlying unique biochemistry and physiology in eukaryotic cells. The ER protein PDZD8 is required for the formation of MERCS in many cell types, however, its tethering partner on the outer mitochondrial membrane (OMM) is currently unknown. Here we identified the OMM protein FKBP8 as the tethering partner of PDZD8 using a combination of unbiased proximity proteomics, CRISPR-Cas9 endogenous protein tagging, Cryo-Electron Microscopy (Cryo-EM) tomography, and correlative light-EM (CLEM). Single molecule tracking revealed highly dynamic diffusion properties of PDZD8 along the ER membrane with significant pauses and capture at MERCS. Overexpression of FKBP8 was sufficient to narrow the ER-OMM distance, whereas independent versus combined deletions of these two proteins demonstrated their interdependence for MERCS formation. Furthermore, PDZD8 enhances mitochondrial complexity in a FKBP8-dependent manner. Our results identify a novel ER-mitochondria tethering complex that regulates mitochondrial morphology in mammalian cells.

线粒体-ER 膜接触点(MERCS)是真核细胞独特的生物化学和生理学的基本超微结构特征。在许多细胞类型中,ER 蛋白 PDZD8 是 MERCS 形成所必需的,但它在线粒体外膜(OMM)上的系链伙伴目前尚不清楚。在这里,我们利用无偏接近蛋白质组学、CRISPR-Cas9 内源蛋白标记、低温电子显微镜(Cryo-EM)层析成像和相关光电子能谱(CLEM)相结合的方法,确定了线粒体外膜蛋白 FKBP8 是 PDZD8 的系链伙伴。单分子追踪显示了 PDZD8 沿 ER 膜的高度动态扩散特性,在 MERCS 处有明显的停顿和捕获。FKBP8的过表达足以缩小ER-OMM的距离,而这两种蛋白的独立缺失和联合缺失则证明了它们在MERCS形成过程中的相互依赖关系。此外,PDZD8以一种依赖于FKBP8的方式增强了线粒体的复杂性。我们的研究结果发现了一种新型的ER-线粒体系链复合体,它能调节哺乳动物细胞中线粒体的形态。
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引用次数: 0
Kids: Willkommen auf der ITS 欢迎到重症监护室
Pub Date : 2023-11-15 DOI: 10.1007/s41906-023-2213-4
Peter Nydahl, Maria Brauchle, Teresa Deffner, Andrea Hillen, Alexander Brinkmann, Svenja Dehner, Rolf Dubb, Simon Finkeldei, Birga Gatzweiler, Carsten Hermes, Christian Heyd, Magdalena Hoffmann, Marie-Madlen Jeitziner, Arnold Kaltwasser, Tita Kern, Kathrin Knochel, Lars Krüger, Heiner Melching, Guido Michels, Tilmann Müller-Wolff, Sabrina Pelz, Julian Rudolph, Denise Schindele, Anna-Henrikje Seidlein, Marina Ufelmann
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引用次数: 0
ChatGPT - Die Lösung gegen den Pflegenotstand? 寄养家庭解决方案?
Pub Date : 2023-11-15 DOI: 10.1007/s41906-023-2208-1
Marcello Ciarrettino
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引用次数: 0
Forschung & Lehre 研究与教学
Pub Date : 2023-11-15 DOI: 10.1007/s41906-023-2191-6
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引用次数: 0
Pflegende Angehörige in der häuslichen Intensivpflege 家庭护理护理家属
Pub Date : 2023-11-15 DOI: 10.1007/s41906-023-2205-4
Yvonne Lehmann
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引用次数: 0
Von innen stärken - aber wie? 利用内心的力量但是怎么利用?
Pub Date : 2023-11-15 DOI: 10.1007/s41906-023-2200-9
Nele Nissen
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引用次数: 0
Report Pflege Aktuell 当前护理报告
Pub Date : 2023-11-15 DOI: 10.1007/s41906-023-2216-1
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引用次数: 0
Der Newsletter des BLGS 布拉特是我们需要的宇航员
Pub Date : 2023-11-15 DOI: 10.1007/s41906-023-2210-7
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引用次数: 0
Politik & Management 政治,管理
Pub Date : 2023-11-15 DOI: 10.1007/s41906-023-2192-5
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引用次数: 0
Pflege Markt 护理市场
Pub Date : 2023-11-15 DOI: 10.1007/s41906-023-2207-2
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引用次数: 0
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Pflege Zeitschrift
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