Cellular prion protein dysfunction in a prototypical inherited metabolic myopathy.
Cell Mol Life Sci
; 78(5): 2157-2167, 2021 Mar.
Article
in En
| MEDLINE
| ID: mdl-32875355
ABSTRACT
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 PrPC, which directly arise from the failure in CPT2 enzymatic activity. We also demonstrate that the loss of PrPC 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 PrPC 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 PrPC in diverse physiopathological situations.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Carnitine O-Palmitoyltransferase
/
Muscle Fibers, Skeletal
/
Focal Adhesions
/
Prion Proteins
/
Muscular Diseases
Limits:
Animals
/
Humans
Language:
En
Journal:
Cell Mol Life Sci
Journal subject:
BIOLOGIA MOLECULAR
Year:
2021
Type:
Article
Affiliation country:
France