Quantitative assessment of mitochondrial morphology relevant for studies on cellular health and environmental toxicity
Mitochondria are essential organelles that play crucial roles in cellular energy metabolism, calcium signaling and apoptosis. Their importance in tissue homeostasis and stress responses, combined to their ability to transition between various structural and functional states, make them excellent org...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-01-01
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| Series: | Computational and Structural Biotechnology Journal |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2001037023004300 |
| _version_ | 1797384068485087232 |
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| author | Sophie Charrasse Titouan Poquillon Charlotte Saint-Omer Manuela Pastore Benoit Bordignon Richard E. Frye Christelle Reynes Victor Racine Abdel Aouacheria |
| author_facet | Sophie Charrasse Titouan Poquillon Charlotte Saint-Omer Manuela Pastore Benoit Bordignon Richard E. Frye Christelle Reynes Victor Racine Abdel Aouacheria |
| author_sort | Sophie Charrasse |
| collection | DOAJ |
| description | Mitochondria are essential organelles that play crucial roles in cellular energy metabolism, calcium signaling and apoptosis. Their importance in tissue homeostasis and stress responses, combined to their ability to transition between various structural and functional states, make them excellent organelles for monitoring cellular health. Quantitative assessment of mitochondrial morphology can therefore provide valuable insights into environmentally-induced cell damage.High-content screening (HCS) provides a powerful tool for analyzing organelles and cellular substructures. We developed a fully automated and miniaturized HCS wet-plus-dry pipeline (MITOMATICS) exploiting mitochondrial morphology as a marker for monitoring cellular health or damage. MITOMATICS uses an in-house, proprietary software (MitoRadar) to enable fast, exhaustive and cost-effective analysis of mitochondrial morphology and its inherent diversity in live cells.We applied our pipeline and big data analytics software to assess the mitotoxicity of selected chemicals, using the mitochondrial uncoupler CCCP as an internal control. Six different pesticides (inhibiting complexes I, II and III of the mitochondrial respiratory chain) were tested as individual compounds and five other pesticides present locally in Occitanie (Southern France) were assessed in combination to determine acute mitotoxicity. Our results show that the assayed pesticides exhibit specific signatures when used as single compounds or chemical mixtures and that they function synergistically to impact mitochondrial architecture.Study of environment-induced mitochondrial damage has the potential to open new fields in mechanistic toxicology, currently underexplored by regulatory toxicology and exposome research. Such exploration could inform health policy guidelines and foster pharmacological intervention, water, air and soil pollution control and food safety. |
| first_indexed | 2024-03-08T21:30:09Z |
| format | Article |
| id | doaj.art-6e14ec44181243a2a8d9451fd078c5e5 |
| institution | Directory Open Access Journal |
| issn | 2001-0370 |
| language | English |
| last_indexed | 2024-03-08T21:30:09Z |
| publishDate | 2023-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Computational and Structural Biotechnology Journal |
| spelling | doaj.art-6e14ec44181243a2a8d9451fd078c5e52023-12-21T07:32:31ZengElsevierComputational and Structural Biotechnology Journal2001-03702023-01-012156095619Quantitative assessment of mitochondrial morphology relevant for studies on cellular health and environmental toxicitySophie Charrasse0Titouan Poquillon1Charlotte Saint-Omer2Manuela Pastore3Benoit Bordignon4Richard E. Frye5Christelle Reynes6Victor Racine7Abdel Aouacheria8Institut des Sciences de l′Evolution de Montpellier (ISEM, UMR 5554, CNRS/UM/IRD/EPHE), Université de Montpellier, Montpellier, FranceInstitut des Sciences de l′Evolution de Montpellier (ISEM, UMR 5554, CNRS/UM/IRD/EPHE), Université de Montpellier, Montpellier, France; QuantaCell SAS, Hôpital Saint Eloi, IRMB, 80 avenue Augustin Fliche, 34090 Montpellier, FranceInstitut des Sciences de l′Evolution de Montpellier (ISEM, UMR 5554, CNRS/UM/IRD/EPHE), Université de Montpellier, Montpellier, FranceSTATABIO BioCampus, Univ. Montpellier, CNRS, INSERM, Montpellier, FranceMontpellier Ressources Imagerie, BioCampus, University of Montpellier, CNRS, INSERM, Montpellier, FranceAutism Discovery and Treatment Foundation, Phoenix, AZ, USASTATABIO BioCampus, Univ. Montpellier, CNRS, INSERM, Montpellier, France; IGF, Univ. Montpellier, CNRS, INSERM, Montpellier, FranceQuantaCell SAS, Hôpital Saint Eloi, IRMB, 80 avenue Augustin Fliche, 34090 Montpellier, FranceInstitut des Sciences de l′Evolution de Montpellier (ISEM, UMR 5554, CNRS/UM/IRD/EPHE), Université de Montpellier, Montpellier, France; Corresponding author.Mitochondria are essential organelles that play crucial roles in cellular energy metabolism, calcium signaling and apoptosis. Their importance in tissue homeostasis and stress responses, combined to their ability to transition between various structural and functional states, make them excellent organelles for monitoring cellular health. Quantitative assessment of mitochondrial morphology can therefore provide valuable insights into environmentally-induced cell damage.High-content screening (HCS) provides a powerful tool for analyzing organelles and cellular substructures. We developed a fully automated and miniaturized HCS wet-plus-dry pipeline (MITOMATICS) exploiting mitochondrial morphology as a marker for monitoring cellular health or damage. MITOMATICS uses an in-house, proprietary software (MitoRadar) to enable fast, exhaustive and cost-effective analysis of mitochondrial morphology and its inherent diversity in live cells.We applied our pipeline and big data analytics software to assess the mitotoxicity of selected chemicals, using the mitochondrial uncoupler CCCP as an internal control. Six different pesticides (inhibiting complexes I, II and III of the mitochondrial respiratory chain) were tested as individual compounds and five other pesticides present locally in Occitanie (Southern France) were assessed in combination to determine acute mitotoxicity. Our results show that the assayed pesticides exhibit specific signatures when used as single compounds or chemical mixtures and that they function synergistically to impact mitochondrial architecture.Study of environment-induced mitochondrial damage has the potential to open new fields in mechanistic toxicology, currently underexplored by regulatory toxicology and exposome research. Such exploration could inform health policy guidelines and foster pharmacological intervention, water, air and soil pollution control and food safety.http://www.sciencedirect.com/science/article/pii/S2001037023004300MitochondriaQuantitative imagingCellular stressConfocal microscopyHigh content analysisLive-cell imaging |
| spellingShingle | Sophie Charrasse Titouan Poquillon Charlotte Saint-Omer Manuela Pastore Benoit Bordignon Richard E. Frye Christelle Reynes Victor Racine Abdel Aouacheria Quantitative assessment of mitochondrial morphology relevant for studies on cellular health and environmental toxicity Computational and Structural Biotechnology Journal Mitochondria Quantitative imaging Cellular stress Confocal microscopy High content analysis Live-cell imaging |
| title | Quantitative assessment of mitochondrial morphology relevant for studies on cellular health and environmental toxicity |
| title_full | Quantitative assessment of mitochondrial morphology relevant for studies on cellular health and environmental toxicity |
| title_fullStr | Quantitative assessment of mitochondrial morphology relevant for studies on cellular health and environmental toxicity |
| title_full_unstemmed | Quantitative assessment of mitochondrial morphology relevant for studies on cellular health and environmental toxicity |
| title_short | Quantitative assessment of mitochondrial morphology relevant for studies on cellular health and environmental toxicity |
| title_sort | quantitative assessment of mitochondrial morphology relevant for studies on cellular health and environmental toxicity |
| topic | Mitochondria Quantitative imaging Cellular stress Confocal microscopy High content analysis Live-cell imaging |
| url | http://www.sciencedirect.com/science/article/pii/S2001037023004300 |
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