Principal component analysis showed a clear separation between FRDA and control samples. Interactome analysis revealed clustering of DE proteins in oxidative phosphorylation, ribosomal elements, mitochondrial architecture control and fission/fusion pathways. DE findings in the muscle-specific proteomics suggested a shift towards fasttwitching glycolytic fibers. Notably, most DE proteins (169/228, 74%) are target of the transcription factor nuclear factor-erythroid 2.Our data corroborate a 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 a likely adaptive 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.
Thursday, October 12, 2023
Skeletal muscle proteome analysis underpins multifaceted mitochondrial dysfunction in Friedreich´s Ataxia
Elisabetta Indelicato, Klaus Faserl, Matthias Amprosi, Wolfgang Nachbauer, Rainer Schneider, Julia Wanschitz, Bettina Sarg, Sylvia Boesch. Skeletal muscle proteome analysis underpins multifaceted mitochondrial dysfunction in Friedreich´s Ataxia; Front. Neurosci. Sec. Neuropharmacology Volume 17 - 2023 | doi: 10.3389/fnins.2023.1289027.
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