Liver CYP4A autophagic lysosomal degradation: A major role for the autophagic receptor SQSTM1/p62 through an uncommon target interaction site.

ABSTRACT: The hepatic P450 hemoproteins CYPs 4A are typical N-terminally anchored type I endoplasmic reticulum (ER) proteins, inducible by many hypolipidemic drugs and peroxisome proliferators. They are engaged in the ω-/ω-1-oxidation of various fatty acids including arachidonic acid, prostaglandins, and leukotrienes and in the biotransformation of some therapeutic drugs. Because the proteolytic turnover of the mammalian liver CYPs 4A remains obscure, we have characterized it. We report that of these proteins, human CYP4A11 and mouse Cyp4a12a are preferential targets of the ER-lysosome-associated degradation. Consequently, these proteins are stabilized 2- to 3-fold both as 1%Triton X100-soluble and insoluble species in mouse hepatocytes and HepG2 cells deficient in the autophagic initiation ATG5 gen

SUBMITTER: He L 

PROVIDER: S-EPMC12597595 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature