Computational classification of mitochondrial shapes reflects stress and redox state.

Computational classification of mitochondrial shapes reflects stress and redox state.
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DOI:
10.1038/cddis.2012.213
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发表时间:
2013-01-17
影响因子:
9
通讯作者:
--
中科院分区:
生物学1区
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--
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线粒体形状的动态变化与功能有关。然而,缺乏自动分类和枚举线粒体形状的工具,也缺乏探索这些形状与线粒体应激关系的系统研究。在这里,我们表明,在线粒体活性氧(mtROS)的产生增加,线粒体改变其形状从管状甜甜圈或斑点的形式,这可以计算量化。用鱼藤酮或抗霉素处理的细胞的成像显示管状形式向甜甜圈形线粒体的时间和剂量依赖性转化,随后出现斑点形式。延时图像显示了从管状到甜甜圈形状的可逆转变以及甜甜圈和斑点形状之间的单向转变。斑点是线粒体ROS的主要来源,似乎与细胞钙内流有关。线粒体形状的变化可以通过预处理抗氧化剂如N-乙酰半胱氨酸或抑制线粒体钙单向转运蛋白来防止。这项工作代表了一种新的方法,通过整合细胞标志物和一种新的形状分类算法,将线粒体的形状与功能联系起来。
Dynamic variations in mitochondrial shape have been related to function. However, tools to automatically classify and enumerate mitochondrial shapes are lacking, as are systematic studies exploring the relationship of such shapes to mitochondrial stress. Here we show that during increased generation of mitochondrial reactive oxygen species (mtROS), mitochondria change their shape from tubular to donut or blob forms, which can be computationally quantified. Imaging of cells treated with rotenone or antimycin, showed time and dose-dependent conversion of tubular forms to donut-shaped mitochondria followed by appearance of blob forms. Time-lapse images showed reversible transitions from tubular to donut shapes and unidirectional transitions between donut and blob shapes. Blobs were the predominant sources of mtROS and appeared to be related to mitochondrial-calcium influx. Mitochondrial shape change could be prevented by either pretreatment with antioxidants like N-acetyl cysteine or inhibition of the mitochondrial calcium uniporter. This work represents a novel approach towards relating mitochondrial shape to function, through integration of cellular markers and a novel shape classification algorithm.
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