Mitochondria transplantation between living cells.
Mitochondria transplantation between living cells.
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DOI：
10.1371/journal.pbio.3001576
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发表时间：
2022-03
期刊：
影响因子：
9.8
通讯作者：
Vorholt JA
中科院分区：
文献类型：
--
作者：
Gäbelein CG;Feng Q;Sarajlic E;Zambelli T;Guillaume-Gentil O;Kornmann B;Vorholt JA
线粒体和复杂的内膜系统是真核细胞的标志。迄今为止，在单个活细胞内操纵细胞器结构一直是困难的。我们开发了一种基于FluidFM的方法，以亚细胞空间分辨率从活细胞中提取、注射和移植细胞器。该技术结合了原子力显微镜、光学显微镜和纳米流体技术，可实现力和体积控制以及实时检测。我们开发了专用探针，允许微创进入细胞和优化流体流动以提取特定细胞器。当提取单个或限定数量的线粒体时，由于局部施加的流体力，它们的形态转化为珍珠串表型。我们表明，诱导的过渡是钙独立的，并在孤立的，完整的线粒体的结果。在细胞间移植时，转移的线粒体融合到宿主细胞线粒体网络。将健康和药物损伤的线粒体移植到原代角质形成细胞中可以监测线粒体亚群的拯救。与受体细胞的线粒体网络的融合发生在移植后20分钟，并持续超过16小时。在转移线粒体和细胞繁殖几代之后，供体线粒体DNA（mtDNA）在受体细胞中复制，而不需要选择压力。这种方法为细胞器生理学和稳态的研究开辟了新的前景，也为治疗，机械生物学和合成生物学开辟了新的前景。线粒体和复杂的内膜系统是真核细胞的标志，但已证明难以操纵单个活细胞内的细胞器结构。本研究描述了一种新的微流体装置，允许从活细胞中提取细胞器，包括线粒体，并将其重新引入受体宿主细胞。
Mitochondria and the complex endomembrane system are hallmarks of eukaryotic cells. To date, it has been difficult to manipulate organelle structures within single live cells. We developed a FluidFM-based approach to extract, inject, and transplant organelles from and into living cells with subcellular spatial resolution. The technology combines atomic force microscopy, optical microscopy, and nanofluidics to achieve force and volume control with real-time inspection. We developed dedicated probes that allow minimally invasive entry into cells and optimized fluid flow to extract specific organelles. When extracting single or a defined number of mitochondria, their morphology transforms into a pearls-on-a-string phenotype due to locally applied fluidic forces. We show that the induced transition is calcium independent and results in isolated, intact mitochondria. Upon cell-to-cell transplantation, the transferred mitochondria fuse to the host cells mitochondrial network. Transplantation of healthy and drug-impaired mitochondria into primary keratinocytes allowed monitoring of mitochondrial subpopulation rescue. Fusion with the mitochondrial network of recipient cells occurred 20 minutes after transplantation and continued for over 16 hours. After transfer of mitochondria and cell propagation over generations, donor mitochondrial DNA (mtDNA) was replicated in recipient cells without the need for selection pressure. The approach opens new prospects for the study of organelle physiology and homeostasis, but also for therapy, mechanobiology, and synthetic biology. Mitochondria and the complex endomembrane system are hallmarks of eukaryotic cells, but it has proved difficult to manipulate organelle structures within single live cells. This study describes a novel microfluidic device that allows the extraction of organelles, including mitochondria, from viable cells and their reintroduction into recipient host cells.
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影响因子：
64.5
作者：
Guillaume-Gentil, Orane;Grindberg, Rashel V.;Vorholt, Julia A.
通讯作者：
Vorholt, Julia A.
影响因子：
7.4
作者：
Guillaume-Gentil, Orane;Rey, Timo;Vorholt, Julia A.
通讯作者：
Vorholt, Julia A.
内质网介导骨细胞树突网络内的线粒体转移
影响因子：
13.6
作者：
Gao, Junjie;Qin, An;Zheng, Ming H.
通讯作者：
Zheng, Ming H.
影响因子：
8.6
作者：
Gonzalez-Rodriguez, David;Sart, Sebastien;Husson, Julien
通讯作者：
Husson, Julien
细胞间线粒体向巨噬细胞转移可调节白色脂肪组织稳态，并在肥胖症中受损。
影响因子：
29
作者：
Brestoff JR;Wilen CB;Moley JR;Li Y;Zou W;Malvin NP;Rowen MN;Saunders BT;Ma H;Mack MR;Hykes BL Jr;Balce DR;Orvedahl A;Williams JW;Rohatgi N;Wang X;McAllaster MR;Handley SA;Kim BS;Doench JG;Zinselmeyer BH;Diamond MS;Virgin HW;Gelman AE;Teitelbaum SL
通讯作者：
Teitelbaum SL