TANGO2-related rhabdomyolysis symptoms are associated with abnormal autophagy functioning
Patients with pathogenic variants in the TANGO2 gene suffer from severe and recurrent rhabdomyolysis episodes precipitated by fasting. Autophagy functioning was analyzed in vitro, in primary skeletal myoblasts from TANGO2 patients, in basal and fasting conditions, and TANGO2 mutations were associate...
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| Language: | English |
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Taylor & Francis Group
2024-12-01
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| Series: | Autophagy Reports |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/27694127.2024.2306766 |
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| author | Hortense de Calbiac Sebastian Montealegre Marjolène Straube Solène Renault Hugo Debruge Loïc Chentout Sorana Ciura Apolline Imbard Edouard Le Guillou Anca Marian Nicolas Goudin Laure Caccavelli Sylvie Fabrega Arnaud Hubas Peter van Endert Nicolas Dupont Julien Diana Edor Kabashi Pascale de Lonlay |
| author_facet | Hortense de Calbiac Sebastian Montealegre Marjolène Straube Solène Renault Hugo Debruge Loïc Chentout Sorana Ciura Apolline Imbard Edouard Le Guillou Anca Marian Nicolas Goudin Laure Caccavelli Sylvie Fabrega Arnaud Hubas Peter van Endert Nicolas Dupont Julien Diana Edor Kabashi Pascale de Lonlay |
| author_sort | Hortense de Calbiac |
| collection | DOAJ |
| description | Patients with pathogenic variants in the TANGO2 gene suffer from severe and recurrent rhabdomyolysis episodes precipitated by fasting. Autophagy functioning was analyzed in vitro, in primary skeletal myoblasts from TANGO2 patients, in basal and fasting conditions, and TANGO2 mutations were associated with reduced LC3-II levels upon starvation. In zebrafish larvae, tango2 inhibition induced locomotor defects which were exacerbated by exposure to atorvastatin, a compound known to cause rhabdomyolysis. Importantly, rhabdomyolysis features of tango2 knockdown were associated with autophagy and mitophagy defects in zebrafish. Calpeptin treatment was sufficient to rescue the locomotor properties thanks to its beneficial effect on autophagy functioning in zebrafish and to improve LC3-II levels in starved primary muscle cells of TANGO2 patients. Overall, we demonstrated that TANGO2 plays an important role in autophagy thus giving rise to new therapeutic perspectives in the prevention of RM life-threatening episodes. |
| format | Article |
| id | doaj-art-4aa5bc2b72924f759db819530d580f6e |
| institution | Kabale University |
| issn | 2769-4127 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Autophagy Reports |
| spelling | doaj-art-4aa5bc2b72924f759db819530d580f6e2024-12-09T07:19:32ZengTaylor & Francis GroupAutophagy Reports2769-41272024-12-013110.1080/27694127.2024.2306766TANGO2-related rhabdomyolysis symptoms are associated with abnormal autophagy functioningHortense de Calbiac0Sebastian Montealegre1Marjolène Straube2Solène Renault3Hugo Debruge4Loïc Chentout5Sorana Ciura6Apolline Imbard7Edouard Le Guillou8Anca Marian9Nicolas Goudin10Laure Caccavelli11Sylvie Fabrega12Arnaud Hubas13Peter van Endert14Nicolas Dupont15Julien Diana16Edor Kabashi17Pascale de Lonlay18Université Paris Cité, INSERM, CNRS, Institut Necker Enfants Malades, F-75015 Paris, FranceUniversité Paris Cité, INSERM, CNRS, Institut Necker Enfants Malades, F-75015 Paris, FranceUniversité Paris Cité, INSERM, CNRS, Institut Necker Enfants Malades, F-75015 Paris, FranceUniversité Paris Cité, INSERM, CNRS, Institut Necker Enfants Malades, F-75015 Paris, FranceUniversité Paris Cité, INSERM, CNRS, Institut Necker Enfants Malades, F-75015 Paris, FranceUniversité Paris Cité, INSERM, CNRS, Institut Necker Enfants Malades, F-75015 Paris, FranceTranslational Research for Neurological Diseases, Institut Imagine, INSERM UMR 1163, Université Paris Cité, F-75015, Paris, FranceMetabolic biochemistry, Hôpital Universitaire Necker-Enfants Malades, AP-HP, Institut Imagine, Filière G2M, MetabERN, Université Paris Cité, F-75015, Paris, FranceMetabolic biochemistry, Hôpital Universitaire Necker-Enfants Malades, AP-HP, Institut Imagine, Filière G2M, MetabERN, Université Paris Cité, F-75015, Paris, FranceTranslational Research for Neurological Diseases, Institut Imagine, INSERM UMR 1163, Université Paris Cité, F-75015, Paris, FranceCell Imaging & Flow Cytometry Core Facilities, Structure Fédérative de Recherche Necker, INSERM US24/CNRS UMS3633, F-75015, FranceUniversité Paris Cité, INSERM, CNRS, Institut Necker Enfants Malades, F-75015 Paris, FrancePlatform, Structure Fédérative de Recherche Necker, F-75015, Paris, FranceGenetics and Molecular Biology, Laboratoire de culture cellulaire, Hôpital Universitaire Cochin, AP-HP, F-75014, Paris, FranceUniversité Paris Cité, INSERM, CNRS, Institut Necker Enfants Malades, F-75015 Paris, FranceUniversité Paris Cité, INSERM, CNRS, Institut Necker Enfants Malades, F-75015 Paris, FranceUniversité Paris Cité, INSERM, CNRS, Institut Necker Enfants Malades, F-75015 Paris, FranceTranslational Research for Neurological Diseases, Institut Imagine, INSERM UMR 1163, Université Paris Cité, F-75015, Paris, FranceUniversité Paris Cité, INSERM, CNRS, Institut Necker Enfants Malades, F-75015 Paris, FrancePatients with pathogenic variants in the TANGO2 gene suffer from severe and recurrent rhabdomyolysis episodes precipitated by fasting. Autophagy functioning was analyzed in vitro, in primary skeletal myoblasts from TANGO2 patients, in basal and fasting conditions, and TANGO2 mutations were associated with reduced LC3-II levels upon starvation. In zebrafish larvae, tango2 inhibition induced locomotor defects which were exacerbated by exposure to atorvastatin, a compound known to cause rhabdomyolysis. Importantly, rhabdomyolysis features of tango2 knockdown were associated with autophagy and mitophagy defects in zebrafish. Calpeptin treatment was sufficient to rescue the locomotor properties thanks to its beneficial effect on autophagy functioning in zebrafish and to improve LC3-II levels in starved primary muscle cells of TANGO2 patients. Overall, we demonstrated that TANGO2 plays an important role in autophagy thus giving rise to new therapeutic perspectives in the prevention of RM life-threatening episodes.https://www.tandfonline.com/doi/10.1080/27694127.2024.2306766AutophagycalpeptinmyoblastsrhabdomyolysisTANGO2zebrafish |
| spellingShingle | Hortense de Calbiac Sebastian Montealegre Marjolène Straube Solène Renault Hugo Debruge Loïc Chentout Sorana Ciura Apolline Imbard Edouard Le Guillou Anca Marian Nicolas Goudin Laure Caccavelli Sylvie Fabrega Arnaud Hubas Peter van Endert Nicolas Dupont Julien Diana Edor Kabashi Pascale de Lonlay TANGO2-related rhabdomyolysis symptoms are associated with abnormal autophagy functioning Autophagy Reports Autophagy calpeptin myoblasts rhabdomyolysis TANGO2 zebrafish |
| title | TANGO2-related rhabdomyolysis symptoms are associated with abnormal autophagy functioning |
| title_full | TANGO2-related rhabdomyolysis symptoms are associated with abnormal autophagy functioning |
| title_fullStr | TANGO2-related rhabdomyolysis symptoms are associated with abnormal autophagy functioning |
| title_full_unstemmed | TANGO2-related rhabdomyolysis symptoms are associated with abnormal autophagy functioning |
| title_short | TANGO2-related rhabdomyolysis symptoms are associated with abnormal autophagy functioning |
| title_sort | tango2 related rhabdomyolysis symptoms are associated with abnormal autophagy functioning |
| topic | Autophagy calpeptin myoblasts rhabdomyolysis TANGO2 zebrafish |
| url | https://www.tandfonline.com/doi/10.1080/27694127.2024.2306766 |
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