Imaging flow cytometry reveals divergent mitochondrial phenotypes in mitochondrial disease patients
Summary: Traditional classification by clinical phenotype or oxidative phosphorylation (OXPHOS) complex deficiencies often fails to clarify complex genotype-phenotype correlations in mitochondrial disease. A multimodal functional assessment may better reveal underlying disease patterns. Using imagin...
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| Format: | Article |
| Language: | English |
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Elsevier
2025-01-01
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| Series: | iScience |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004224027238 |
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| author | Irena.J.J. Muffels Richard Rodenburg Hanneke L.D. Willemen Désirée van Haaften-Visser Hans Waterham Niels Eijkelkamp Sabine A. Fuchs Peter M. van Hasselt |
| author_facet | Irena.J.J. Muffels Richard Rodenburg Hanneke L.D. Willemen Désirée van Haaften-Visser Hans Waterham Niels Eijkelkamp Sabine A. Fuchs Peter M. van Hasselt |
| author_sort | Irena.J.J. Muffels |
| collection | DOAJ |
| description | Summary: Traditional classification by clinical phenotype or oxidative phosphorylation (OXPHOS) complex deficiencies often fails to clarify complex genotype-phenotype correlations in mitochondrial disease. A multimodal functional assessment may better reveal underlying disease patterns. Using imaging flow cytometry (IFC), we evaluated mitochondrial fragmentation, swelling, membrane potential, reactive oxygen species (ROS) production, and mitochondrial mass in fibroblasts from 31 mitochondrial disease patients. Significant changes were observed in 97% of patients, forming two overarching groups with distinct responses to mitochondrial pathology. One group displayed low-to-normal membrane potential, indicating a hypometabolic state, while the other showed elevated membrane potential and swelling, suggesting a hypermetabolic state. Literature analysis linked these clusters to complex I stability defects (hypometabolic) and proton pumping activity (hypermetabolic). Thus, our IFC-based platform offers a novel approach to identify disease-specific patterns through functional responses, supporting improved diagnostic and therapeutic strategies. |
| format | Article |
| id | doaj-art-290d486bf0a14e91ba0c8e0150a08f47 |
| institution | OA Journals |
| issn | 2589-0042 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj-art-290d486bf0a14e91ba0c8e0150a08f472025-08-20T02:36:58ZengElsevieriScience2589-00422025-01-0128111149610.1016/j.isci.2024.111496Imaging flow cytometry reveals divergent mitochondrial phenotypes in mitochondrial disease patientsIrena.J.J. Muffels0Richard Rodenburg1Hanneke L.D. Willemen2Désirée van Haaften-Visser3Hans Waterham4Niels Eijkelkamp5Sabine A. Fuchs6Peter M. van Hasselt7Department of Metabolic Diseases, Wilhelmina Children’s Hospital, University Medical Center Utrecht, Utrecht 3584 EA, the Netherlands; Corresponding authorNijmegen Center for Mitochondrial Disorders, Radboud University Nijmegen Medical Center, Nijmegen 6525 GA, the NetherlandsCenter for Translational Immunology (CTI), Wilhelmina Children’s Hospital, University Medical Center Utrecht, Utrecht 3584 EA, the NetherlandsDepartment of Pediatrics, Center for Lysosomal and Metabolic Diseases, Erasmus University Medical Center, Rotterdam 3015 GD, the NetherlandsUnited for Metabolic Diseases (UMD), Utrecht 3584 EA, the Netherlands; Department of Laboratory Medicine, Laboratory Genetic Metabolic Diseases, Amsterdam UMC - AMC, Amsterdam 1105 AZ, the NetherlandsCenter for Translational Immunology (CTI), Wilhelmina Children’s Hospital, University Medical Center Utrecht, Utrecht 3584 EA, the NetherlandsDepartment of Metabolic Diseases, Wilhelmina Children’s Hospital, University Medical Center Utrecht, Utrecht 3584 EA, the Netherlands; United for Metabolic Diseases (UMD), Utrecht 3584 EA, the NetherlandsDepartment of Metabolic Diseases, Wilhelmina Children’s Hospital, University Medical Center Utrecht, Utrecht 3584 EA, the Netherlands; United for Metabolic Diseases (UMD), Utrecht 3584 EA, the Netherlands; Corresponding authorSummary: Traditional classification by clinical phenotype or oxidative phosphorylation (OXPHOS) complex deficiencies often fails to clarify complex genotype-phenotype correlations in mitochondrial disease. A multimodal functional assessment may better reveal underlying disease patterns. Using imaging flow cytometry (IFC), we evaluated mitochondrial fragmentation, swelling, membrane potential, reactive oxygen species (ROS) production, and mitochondrial mass in fibroblasts from 31 mitochondrial disease patients. Significant changes were observed in 97% of patients, forming two overarching groups with distinct responses to mitochondrial pathology. One group displayed low-to-normal membrane potential, indicating a hypometabolic state, while the other showed elevated membrane potential and swelling, suggesting a hypermetabolic state. Literature analysis linked these clusters to complex I stability defects (hypometabolic) and proton pumping activity (hypermetabolic). Thus, our IFC-based platform offers a novel approach to identify disease-specific patterns through functional responses, supporting improved diagnostic and therapeutic strategies.http://www.sciencedirect.com/science/article/pii/S2589004224027238Health sciencesMedicineNatural sciencesBiological sciencesGeneticsHuman genetics |
| spellingShingle | Irena.J.J. Muffels Richard Rodenburg Hanneke L.D. Willemen Désirée van Haaften-Visser Hans Waterham Niels Eijkelkamp Sabine A. Fuchs Peter M. van Hasselt Imaging flow cytometry reveals divergent mitochondrial phenotypes in mitochondrial disease patients iScience Health sciences Medicine Natural sciences Biological sciences Genetics Human genetics |
| title | Imaging flow cytometry reveals divergent mitochondrial phenotypes in mitochondrial disease patients |
| title_full | Imaging flow cytometry reveals divergent mitochondrial phenotypes in mitochondrial disease patients |
| title_fullStr | Imaging flow cytometry reveals divergent mitochondrial phenotypes in mitochondrial disease patients |
| title_full_unstemmed | Imaging flow cytometry reveals divergent mitochondrial phenotypes in mitochondrial disease patients |
| title_short | Imaging flow cytometry reveals divergent mitochondrial phenotypes in mitochondrial disease patients |
| title_sort | imaging flow cytometry reveals divergent mitochondrial phenotypes in mitochondrial disease patients |
| topic | Health sciences Medicine Natural sciences Biological sciences Genetics Human genetics |
| url | http://www.sciencedirect.com/science/article/pii/S2589004224027238 |
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