Stentenbach, Maike and Hughes, Laetitia A. and Fagan, Samuel V. and Payne, Blake and Rudler, Danielle L. and Siira, Stefan J. and McCubbin, Tim and Chopin, Anaëlle and Perks, Kara L. and Ermer, Judith A. and Hendry, James and Er, Teagan S. and Balasubramaniam, Shanti and Eliades, Joel A. and Hool, Livia C. and Packer, Nicolle H. and Moh, Edward S. X. and Padman, Benjamin S. and Rackham, Oliver and Filipovska, Aleksandra (2025) TANGO2 binds crystallin alpha B and its loss causes desminopathy. Nature Communications, 16 (1). ISSN 2041-1723
Full text not available from this repository.Abstract
Abstract
Mutations in the TANGO2 gene cause an autosomal recessive disorder characterised by developmental delay, stress-induced episodic rhabdomyolysis, and cardiac arrhythmias along with severe metabolic crises. Although TANGO2 mutations result in a well characterised disease pathology, the function of TANGO2 is still unknown. To investigate the function of TANGO2, we knocked out the TANGO2 gene in human cells and mice. We identify that loss of TANGO2 impairs intermediate filament structure, resulting in fragmented mitochondrial networks and formation of cup-like mitochondria. In male mice, loss of TANGO2 caused heart defects, reduced muscle function and glucose intolerance by remodelling of intermediate filaments, which altered the mitochondrial and cytoplasmic proteomes, N-glycosylation and nucleocytoplasmic O-GlcNAcylation. We identify that TANGO2 binds the small heat shock protein crystallin alpha B (CRYAB) to prevent the aggregation of the intermediate filament desmin and in the absence of TANGO2, mice develop desminopathy, which is consistent with features found in patients carrying mutations in either desmin or CRYAB.
| Item Type: | Article |
|---|---|
| Subjects: | R Medicine > R Medicine (General) |
| Depositing User: | Repository Administrator |
| Date Deposited: | 31 Oct 2025 05:01 |
| Last Modified: | 31 Oct 2025 05:01 |
| URI: | http://eprints.victorchang.edu.au/id/eprint/1726 |
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