PUBLICATION
TANGO2-related rhabdomyolysis symptoms are associated with abnormal autophagy functioning
- Authors
- de Calbiac, H., Montealegre, S., Straube, M., Renault, S., Debruge, H., Chentout, L., Ciura, S., Imbard, A., Guillou, E.L., Marian, A., Goudin, N., Caccavelli, L., Fabrega, S., Hubas, A., van Endert, P., Dupont, N., Diana, J., Kabashi, E., de Lonlay, P.
- ID
- ZDB-PUB-250109-57
- Date
- 2024
- Source
- Autophagy reports 3(1): (Journal)
- Registered Authors
- Keywords
- Autophagy, TANGO2, calpeptin, myoblasts, rhabdomyolysis, zebrafish
- MeSH Terms
- none
- PubMed
- 39722856 Full text @ Autophagy Rep
Citation
de Calbiac, H., Montealegre, S., Straube, M., Renault, S., Debruge, H., Chentout, L., Ciura, S., Imbard, A., Guillou, E.L., Marian, A., Goudin, N., Caccavelli, L., Fabrega, S., Hubas, A., van Endert, P., Dupont, N., Diana, J., Kabashi, E., de Lonlay, P. (2024) TANGO2-related rhabdomyolysis symptoms are associated with abnormal autophagy functioning. Autophagy reports. 3(1):.
Abstract
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping