mito-QC illuminates mitophagy and mitochondrial architecture in vivo.
mito-QC illuminates mitophagy and mitochondrial architecture in vivo.
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DOI：
10.1083/jcb.201603039
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发表时间：
2016-08-01
期刊：
影响因子：
--
通讯作者：
Ganley IG
中科院分区：
文献类型：
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作者：
McWilliams TG;Prescott AR;Allen GF;Tamjar J;Munson MJ;Thomson C;Muqit MM;Ganley IG
线粒体自噬是否发生在体内特定的细胞亚型尚不清楚。McWilliams等人提出了“mito-QC”，一种含有pH敏感荧光线粒体信号的转基因小鼠，允许在单细胞分辨率下体内检测线粒体自噬和线粒体形态。线粒体的自噬周转（mitophagic turnover）被称为线粒体自噬（mitophagy），被认为是哺乳动物病理生理相关的一种重要质量控制（QC）机制。然而，线粒体自噬是否以及如何在体内特定的细胞亚型中进行仍然不清楚，主要是因为缺乏易于处理的工具和模型。为了解决这个问题，我们开发了“mito-QC”，一种具有pH敏感荧光线粒体信号的转基因小鼠。这允许在体内评估线粒体自噬和线粒体结构。使用共聚焦显微镜，我们表明，mito-QC是兼容的经典和当代技术在组织化学，并允许明确的体内检测线粒体自噬和线粒体形态在多个器官系统内的单细胞分辨率。引人注目的是，我们的模型揭示了发育中的心脏和成人肾脏特定细胞内高度富集和差异化的线粒体自噬区。mito-QC是一种实验上有利的工具，与基于发现和转化研究社区的细胞生物学研究人员具有广泛的相关性。
Whether mitophagy occurs within specific cellular subtypes in vivo is unclear. McWilliams et al. present “mito-QC,” a transgenic mouse containing a pH-sensitive fluorescent mitochondrial signal, allowing in vivo detection of mitophagy and mitochondrial morphology at single-cell resolution. Autophagic turnover of mitochondria, termed mitophagy, is proposed to be an essential quality-control (QC) mechanism of pathophysiological relevance in mammals. However, if and how mitophagy proceeds within specific cellular subtypes in vivo remains unclear, largely because of a lack of tractable tools and models. To address this, we have developed “mito-QC,” a transgenic mouse with a pH-sensitive fluorescent mitochondrial signal. This allows the assessment of mitophagy and mitochondrial architecture in vivo. Using confocal microscopy, we demonstrate that mito-QC is compatible with classical and contemporary techniques in histochemistry and allows unambiguous in vivo detection of mitophagy and mitochondrial morphology at single-cell resolution within multiple organ systems. Strikingly, our model uncovers highly enriched and differential zones of mitophagy in the developing heart and within specific cells of the adult kidney. mito-QC is an experimentally advantageous tool of broad relevance to cell biology researchers within both discovery-based and translational research communities.