Misfolding, degradation, and aggregation of variant proteins. The molecular pathogenesis of short chain acyl-CoA dehydrogenase (SCAD) deficiency
Pedersen, C.Bak.; Bross, P.; Winter, V.Stenbroen.; Corydon, T.Juhl.; Bolund, L.; Bartlett, K.; Vockley, J.; Gregersen, N.
Journal of Biological Chemistry 278(48): 47449-47458
ISSN/ISBN: 0021-9258 PMID: 14506246 DOI: 10.1074/jbc.m309514200
Short chain acyl-CoA dehydrogenase (SCAD) deficiency is an inborn error of the mitochondrial fatty acid metabolism caused by rare variations as well as common susceptibility variations in the SCAD gene. Earlier studies have shown that a common variant SCAD protein (R147W) was impaired in folding, and preliminary experiments suggested that the variant protein displayed prolonged association with chaperonins and delayed formation of active enzyme. Accordingly, the molecular pathogenesis of SCAD deficiency may rely on intramitochondrial protein quality control mechanisms, including degradation and aggregation of variant SCAD proteins.