Multi-parametric analysis and modeling of relationships between mitochondrial morphology and apoptosis.

Mitochondria exist as a network of interconnected organelles undergoing constant fission and fusion. Current approaches to study mitochondrial morphology are limited by low data sampling coupled with manual identification and classification of complex morphological phenotypes. Here we propose an int...

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Autores principales:	Yara Reis, Marti Bernardo-Faura, Daniela Richter, Thomas Wolf, Benedikt Brors, Anne Hamacher-Brady, Roland Eils, Nathan R Brady
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/a438262b7094474a88ff7673445cd740
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spelling	oai:doaj.org-article:a438262b7094474a88ff7673445cd7402021-11-18T07:30:15ZMulti-parametric analysis and modeling of relationships between mitochondrial morphology and apoptosis.1932-620310.1371/journal.pone.0028694https://doaj.org/article/a438262b7094474a88ff7673445cd7402012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22272225/?tool=EBIhttps://doaj.org/toc/1932-6203Mitochondria exist as a network of interconnected organelles undergoing constant fission and fusion. Current approaches to study mitochondrial morphology are limited by low data sampling coupled with manual identification and classification of complex morphological phenotypes. Here we propose an integrated mechanistic and data-driven modeling approach to analyze heterogeneous, quantified datasets and infer relations between mitochondrial morphology and apoptotic events. We initially performed high-content, multi-parametric measurements of mitochondrial morphological, apoptotic, and energetic states by high-resolution imaging of human breast carcinoma MCF-7 cells. Subsequently, decision tree-based analysis was used to automatically classify networked, fragmented, and swollen mitochondrial subpopulations, at the single-cell level and within cell populations. Our results revealed subtle but significant differences in morphology class distributions in response to various apoptotic stimuli. Furthermore, key mitochondrial functional parameters including mitochondrial membrane potential and Bax activation, were measured under matched conditions. Data-driven fuzzy logic modeling was used to explore the non-linear relationships between mitochondrial morphology and apoptotic signaling, combining morphological and functional data as a single model. Modeling results are in accordance with previous studies, where Bax regulates mitochondrial fragmentation, and mitochondrial morphology influences mitochondrial membrane potential. In summary, we established and validated a platform for mitochondrial morphological and functional analysis that can be readily extended with additional datasets. We further discuss the benefits of a flexible systematic approach for elucidating specific and general relationships between mitochondrial morphology and apoptosis.Yara ReisMarti Bernardo-FauraDaniela RichterThomas WolfBenedikt BrorsAnne Hamacher-BradyRoland EilsNathan R BradyPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 1, p e28694 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Yara Reis Marti Bernardo-Faura Daniela Richter Thomas Wolf Benedikt Brors Anne Hamacher-Brady Roland Eils Nathan R Brady Multi-parametric analysis and modeling of relationships between mitochondrial morphology and apoptosis.
description	Mitochondria exist as a network of interconnected organelles undergoing constant fission and fusion. Current approaches to study mitochondrial morphology are limited by low data sampling coupled with manual identification and classification of complex morphological phenotypes. Here we propose an integrated mechanistic and data-driven modeling approach to analyze heterogeneous, quantified datasets and infer relations between mitochondrial morphology and apoptotic events. We initially performed high-content, multi-parametric measurements of mitochondrial morphological, apoptotic, and energetic states by high-resolution imaging of human breast carcinoma MCF-7 cells. Subsequently, decision tree-based analysis was used to automatically classify networked, fragmented, and swollen mitochondrial subpopulations, at the single-cell level and within cell populations. Our results revealed subtle but significant differences in morphology class distributions in response to various apoptotic stimuli. Furthermore, key mitochondrial functional parameters including mitochondrial membrane potential and Bax activation, were measured under matched conditions. Data-driven fuzzy logic modeling was used to explore the non-linear relationships between mitochondrial morphology and apoptotic signaling, combining morphological and functional data as a single model. Modeling results are in accordance with previous studies, where Bax regulates mitochondrial fragmentation, and mitochondrial morphology influences mitochondrial membrane potential. In summary, we established and validated a platform for mitochondrial morphological and functional analysis that can be readily extended with additional datasets. We further discuss the benefits of a flexible systematic approach for elucidating specific and general relationships between mitochondrial morphology and apoptosis.
format	article
author	Yara Reis Marti Bernardo-Faura Daniela Richter Thomas Wolf Benedikt Brors Anne Hamacher-Brady Roland Eils Nathan R Brady
author_facet	Yara Reis Marti Bernardo-Faura Daniela Richter Thomas Wolf Benedikt Brors Anne Hamacher-Brady Roland Eils Nathan R Brady
author_sort	Yara Reis
title	Multi-parametric analysis and modeling of relationships between mitochondrial morphology and apoptosis.
title_short	Multi-parametric analysis and modeling of relationships between mitochondrial morphology and apoptosis.
title_full	Multi-parametric analysis and modeling of relationships between mitochondrial morphology and apoptosis.
title_fullStr	Multi-parametric analysis and modeling of relationships between mitochondrial morphology and apoptosis.
title_full_unstemmed	Multi-parametric analysis and modeling of relationships between mitochondrial morphology and apoptosis.
title_sort	multi-parametric analysis and modeling of relationships between mitochondrial morphology and apoptosis.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/a438262b7094474a88ff7673445cd740
work_keys_str_mv	AT yarareis multiparametricanalysisandmodelingofrelationshipsbetweenmitochondrialmorphologyandapoptosis AT martibernardofaura multiparametricanalysisandmodelingofrelationshipsbetweenmitochondrialmorphologyandapoptosis AT danielarichter multiparametricanalysisandmodelingofrelationshipsbetweenmitochondrialmorphologyandapoptosis AT thomaswolf multiparametricanalysisandmodelingofrelationshipsbetweenmitochondrialmorphologyandapoptosis AT benediktbrors multiparametricanalysisandmodelingofrelationshipsbetweenmitochondrialmorphologyandapoptosis AT annehamacherbrady multiparametricanalysisandmodelingofrelationshipsbetweenmitochondrialmorphologyandapoptosis AT rolandeils multiparametricanalysisandmodelingofrelationshipsbetweenmitochondrialmorphologyandapoptosis AT nathanrbrady multiparametricanalysisandmodelingofrelationshipsbetweenmitochondrialmorphologyandapoptosis
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Multi-parametric analysis and modeling of relationships between mitochondrial morphology and apoptosis.

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