Metabolic dysregulation contributes to the development of dysferlinopathy.

ABSTRACT: Dysferlin is a transmembrane protein that plays a prominent role in membrane repair of damaged muscle fibers. Accordingly, mutations in the dysferlin gene cause progressive muscular dystrophies, collectively referred to as dysferlinopathies for which no effective treatment exists. Unexpectedly, experimental approaches that successfully restore membrane repair fail to prevent a dystrophic phenotype, suggesting that additional, hitherto unknown dysferlin-dependent functions contribute to the development of the pathology. Our experiments revealed an altered metabolic phenotype in dysferlin-deficient muscles, characterized by (1) mitochondrial abnormalities and elevated death signaling and (2) increased glucose uptake, reduced glycolytic protein levels, and pronounced glycogen accumulation. St

SUBMITTER: Furrer R 

PROVIDER: S-EPMC11871293 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature