Updated project metadata.
Friedreich´s Ataxia (FRDA) is a severe neuromuscular disorder caused by a deficiency of the mitochondrial protein frataxin. While some aspects of FRDA pathology are developmental, the causes underlying the steady progression are unclear. The inaccessibility of key affected tissues to sampling is a main hurdle. Skeletal muscle displays a disease phenotype and may be sampled in vivo to address open questions on FRDA pathophysiology. We performed a mass spectrometry (MS)-based proteomics analysis in gastrocnemius skeletal muscle biopsies from genetically confirmed FRDA patients (n=5) and controls. Our data corroborate a predominant mitochondrial biosignature of FRDA, which extends beyond a mere oxidative phosphorylation failure. Skeletal muscle proteomics highlighted a derangement of mitochondrial architecture and maintenance pathways and an adaptative metabolic shift of contractile proteins. The present findings are relevant for the design of future therapeutic strategies and highlight the value of skeletal muscle -omics as disease state readout in FRDA.