| First Author | Boufroura FZ | Year | 2021 |
| Journal | Cell Mol Life Sci | Volume | 78 |
| Issue | 5 | Pages | 2157-2167 |
| PubMed ID | 32875355 | Mgi Jnum | J:310490 |
| Mgi Id | MGI:6762744 | Doi | 10.1007/s00018-020-03624-6 |
| Citation | Boufroura FZ, et al. (2021) Cellular prion protein dysfunction in a prototypical inherited metabolic myopathy. Cell Mol Life Sci 78(5):2157-2167 |
| abstractText | Inherited fatty acid oxidation diseases in their mild forms often present as metabolic myopathies. Carnitine Palmitoyl Transferase 2 (CPT2) deficiency, one such prototypical disorder is associated with compromised myotube differentiation. Here, we show that CPT2-deficient myotubes exhibit defects in focal adhesions and redox balance, exemplified by increased SOD2 expression. We document unprecedented alterations in the cellular prion protein PrP(C), which directly arise from the failure in CPT2 enzymatic activity. We also demonstrate that the loss of PrP(C) function in normal myotubes recapitulates the defects in focal adhesion, redox balance and differentiation hallmarks monitored in CPT2-deficient cells. These results are further corroborated by studies performed in muscles from Prnp(-/-) mice. Altogether, our results unveil a molecular scenario, whereby PrP(C) dysfunction governed by faulty CPT2 activity may drive aberrant focal adhesion turnover and hinder proper myotube differentiation. Our study adds a novel facet to the involvement of PrP(C) in diverse physiopathological situations. |
