PEX1^G843D remains functional in peroxisome biogenesis but is rapidly degraded by the proteasome.

ABSTRACT: The PEX1/PEX6 AAA-ATPase is required for the biogenesis and maintenance of peroxisomes. Mutations in HsPEX1 and HsPEX6 disrupt peroxisomal matrix protein import and are the leading cause of Peroxisome Biogenesis Disorders (PBDs). The most common disease-causing mutation in PEX1 is the HsPEX1^G843D allele, which results in a reduction of peroxisomal protein import. Here we demonstrate that in vitro the homologous yeast mutant, ScPex1^G700D, reduces the stability of Pex1's active D2 ATPase domain and impairs assembly with Pex6, but can still form an active AAA-ATPase motor. In vivo, ScPex1^G700D exhibits only a slight defect in peroxisome import. We generated model human HsPEX1^G843D cell lines an

SUBMITTER: Sheedy CJ 

PROVIDER: S-EPMC11661142 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature