title: Automatic morphological subtyping reveals new roles of caspases in mitochondrial dynamics.
abstract: 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.
authors: Institute of Biomedical Informatics, National Yang-Ming University, Taipei, Taiwan. jypeng@ym.edu.tw
authors: Jyh-Ying
authors: JY
authors: Peng
authors: Chung-Chih
authors: CC
authors: Lin
authors: Yen-Jen
authors: YJ
authors: Chen
authors: Lung-Sen
authors: LS
authors: Kao
authors: Young-Chau
authors: YC
authors: Liu
authors: Chung-Chien
authors: CC
authors: Chou
authors: Yi-Hung
authors: YH
authors: Huang
authors: Fang-Rong
authors: FR
authors: Chang
authors: Yang-Chang
authors: YC
authors: Wu
authors: Yuh-Show
authors: YS
authors: Tsai
authors: Chun-Nan
authors: CN
authors: Hsu
mesh_terms: D000818:Animals; D016466:CHO Cells; D061945:Caspase Inhibitors; D020169:Caspases / Q000378:metabolism*; D019295:Computational Biology; D006224:Cricetinae; D003412:Cricetulus; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D005663:Furans / Q000494:pharmacology; D007783:Lactones / Q000494:pharmacology; D008928:Mitochondria / Q000145:classification / Q000187:drug effects / Q000201:enzymology* / Q000648:ultrastructure*; D008954:Models, Biological; D009842:Oligopeptides / Q000494:pharmacology; D010363:Pattern Recognition, Automated / Q000706:statistics & numerical data
chemical_list: D061945:Caspase Inhibitors; D015853:Cysteine Proteinase Inhibitors; D005663:Furans; D007783:Lactones; D009842:Oligopeptides; C403753:benzyloxycarbonyl-isoleucyl-glutamyl-threonyl-aspartic acid fluoromethyl ketone; C403754:benzyloxycarbonyl-leucyl-glutamyl-histidyl-aspartic acid fluoromethyl ketone; C059660:squamocin; D020169:Caspases; D004121:Dimethyl Sulfoxide