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

• Verfasst von: Reis, Yara [VerfasserIn]
• Verfasst von: Bernardo Faura, Martí [VerfasserIn]
• Verfasst von: Richter, Daniela [VerfasserIn]
• Verfasst von: Wolf, Thomas [VerfasserIn]
• Verfasst von: Brors, Benedikt [VerfasserIn]
• Verfasst von: Hamacher-Brady, Anne [VerfasserIn]
• Verfasst von: Eils, Roland [VerfasserIn]
• Verfasst von: Brady, Nathan [VerfasserIn]
• Titel: Multi-parametric analysis and modeling of relationships between mitochondrial morphology and apoptosis
• Verf.angabe: Yara Reis, Marti Bernardo-Faura, Daniela Richter, Thomas Wolf, Benedikt Brors, Anne Hamacher-Brady, Roland Eils, Nathan R. Brady
• E-Jahr: 2012
• Jahr: 17 January 2012
• Fussnoten: Gesehen am 11.05.2018
• Titel Quelle: Enthalten in: PLOS ONE
• Ort Quelle: San Francisco, California, US : PLOS, 2006
• Jahr Quelle: 2012
• Band/Heft Quelle: 7(2012,1) Artikel-Nummer e28694, 19 Seiten
• ISSN Quelle: 1932-6203
• DOI: doi:10.1371/journal.pone.0028694
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: Apoptosis
• Sach-SW: Apoptotic signaling cascade
• Sach-SW: Decision trees
• Sach-SW: Depolarization
• Sach-SW: Drug therapy
• Sach-SW: Membrane potential
• Sach-SW: Mitochondria
• Sach-SW: Mitochondrial membrane
• K10plus-PPN: 1574995804

Abstract

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.