Monitoring mitochondrial translation in living cells.
Monitoring mitochondrial translation in living cells.
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DOI：
10.15252/embr.202051635
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发表时间：
2021-04-07
期刊：
影响因子：
7.7
通讯作者：
Pacheu-Grau D
中科院分区：
文献类型：
--
作者：
Yousefi R;Fornasiero EF;Cyganek L;Montoya J;Jakobs S;Rizzoli SO;Rehling P;Pacheu-Grau D
线粒体拥有一个小的基因组，编码氧化磷酸化系统的核心亚基，其表达对于能量产生至关重要。有关细胞环境中线粒体基因表达的调控和空间组织的信息一直很难获得。在这里，我们设计了一种成像方法，通过合并可点击的非规范氨基酸来分析单细胞背景下的线粒体翻译。我们将该方法应用于多种细胞类型，包括心肌细胞和神经元等特殊细胞，并以空间分辨率监测轴突和树突中的线粒体翻译。我们还表明，翻译成像可以监测患者成纤维细胞中线粒体蛋白的表达。利用点击化学进行线粒体翻译，为了解线粒体生物发生如何整合到细胞环境中开辟了新途径，并可用于评估线粒体疾病中的线粒体基因表达。这项研究以空间分辨率监测多种细胞类型的单细胞中线粒体蛋白质的合成。
Mitochondria possess a small genome that codes for core subunits of the oxidative phosphorylation system and whose expression is essential for energy production. Information on the regulation and spatial organization of mitochondrial gene expression in the cellular context has been difficult to obtain. Here we devise an imaging approach to analyze mitochondrial translation within the context of single cells, by following the incorporation of clickable non‐canonical amino acids. We apply this method to multiple cell types, including specialized cells such as cardiomyocytes and neurons, and monitor with spatial resolution mitochondrial translation in axons and dendrites. We also show that translation imaging allows to monitor mitochondrial protein expression in patient fibroblasts. Approaching mitochondrial translation with click chemistry opens new avenues to understand how mitochondrial biogenesis is integrated into the cellular context and can be used to assess mitochondrial gene expression in mitochondrial diseases. This study monitors mitochondrial protein synthesis with spatial resolution in single cells of multiple cell types.