Institute of Biomedical Informatics, National Yang-Ming University, Taipei, Taiwan.
PLoS Comput Biol. 2011 Oct;7(10):e1002212. doi: 10.1371/journal.pcbi.1002212. Epub 2011 Oct 6.
Morphological dynamics of mitochondria is associated with key cellular processes related to aging and neuronal degenerative diseases, but the lack of standard quantification of mitochondrial morphology impedes systematic investigation. This paper presents an automated system for the quantification and classification of mitochondrial morphology. We discovered six morphological subtypes of mitochondria for objective quantification of mitochondrial morphology. These six subtypes are small globules, swollen globules, straight tubules, twisted tubules, branched tubules and loops. The subtyping was derived by applying consensus clustering to a huge collection of more than 200 thousand mitochondrial images extracted from 1422 micrographs of Chinese hamster ovary (CHO) cells treated with different drugs, and was validated by evidence of functional similarity reported in the literature. Quantitative statistics of subtype compositions in cells is useful for correlating drug response and mitochondrial dynamics. Combining the quantitative results with our biochemical studies about the effects of squamocin on CHO cells reveals new roles of Caspases in the regulatory mechanisms of mitochondrial dynamics. This system is not only of value to the mitochondrial field, but also applicable to the investigation of other subcellular organelle morphology.
线粒体的形态动力学与衰老和神经退行性疾病相关的关键细胞过程有关，但缺乏对线粒体形态的标准量化方法阻碍了系统研究。本文提出了一种用于线粒体形态定量和分类的自动化系统。我们发现了六种线粒体的形态亚型，可用于对线粒体形态进行客观量化。这六种亚型分别是小球体、肿胀球体、直管、扭曲管、分支管和环。通过对从用不同药物处理的中国仓鼠卵巢（CHO）细胞的 1422 张显微照片中提取的超过 20 万个线粒体图像进行共识聚类分析，得出了这六种亚型，并通过文献中报道的功能相似性证据进行了验证。细胞中亚型组成的定量统计有助于将药物反应与线粒体动力学相关联。将定量结果与我们关于 squamocin 对 CHO 细胞影响的生化研究相结合，揭示了 Caspases 在调节线粒体动力学的机制中的新作用。该系统不仅对线粒体领域具有价值，而且适用于其他亚细胞器形态的研究。
