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Automatic morphological subtyping reveals new roles of caspases in mitochondrial dynamics.
- Source :
-
PLoS computational biology [PLoS Comput Biol] 2011 Oct; Vol. 7 (10), pp. e1002212. Date of Electronic Publication: 2011 Oct 06. - Publication Year :
- 2011
-
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.
- Subjects :
- Animals
CHO Cells
Caspase Inhibitors
Computational Biology
Cricetinae
Cricetulus
Cysteine Proteinase Inhibitors pharmacology
Dimethyl Sulfoxide pharmacology
Furans pharmacology
Lactones pharmacology
Mitochondria classification
Mitochondria drug effects
Models, Biological
Oligopeptides pharmacology
Pattern Recognition, Automated statistics & numerical data
Caspases metabolism
Mitochondria enzymology
Mitochondria ultrastructure
Subjects
Details
- Language :
- English
- ISSN :
- 1553-7358
- Volume :
- 7
- Issue :
- 10
- Database :
- MEDLINE
- Journal :
- PLoS computational biology
- Publication Type :
- Academic Journal
- Accession number :
- 21998575
- Full Text :
- https://doi.org/10.1371/journal.pcbi.1002212