Centre for Excellence in Asthma and Lung Disease, CSIR-Institute of Genomics and Integrative Biology, Delhi, India.
Cell Death Dis. 2013 Jan 17;4(1):e461. doi: 10.1038/cddis.2012.213.
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.
线粒体形状的动态变化与功能有关。然而，目前缺乏自动分类和计数线粒体形状的工具，也缺乏系统研究这些形状与线粒体应激关系的研究。在这里，我们展示了在增加线粒体活性氧（mtROS）生成时，线粒体的形状从管状变为环形或块状，可以通过计算进行量化。对用鱼藤酮或抗霉素处理的细胞进行成像，显示出随着时间和剂量的依赖性，管状形式向环形线粒体的转化，然后出现块状形式。延时图像显示了从管状到环形形状的可逆转变以及环形和块状形状之间的单向转变。球形是 mtROS 的主要来源，并且似乎与线粒体钙内流有关。线粒体形状的变化可以通过用抗氧化剂如 N-乙酰半胱氨酸预处理或抑制线粒体钙单向转运体来预防。这项工作代表了一种通过整合细胞标记物和一种新的形状分类算法将线粒体形状与功能联系起来的新方法。
