title: Presecretory oxidation, aggregation, and autophagic destruction of apoprotein-B: a pathway for late-stage quality control.
abstract: Hepatic secretion of apolipoprotein-B (apoB), the major protein of atherogenic lipoproteins, is regulated through posttranslational degradation. We reported a degradation pathway, post-ER pre secretory proteolysis (PERPP), that is increased by reactive oxygen species (ROS) generated within hepatocytes from dietary polyunsaturated fatty acids (PUFA). We now report the molecular processes by which PUFA-derived ROS regulate PERPP of apoB. ApoB exits the ER; undergoes limited oxidant-dependent aggregation; and then, upon exit from the Golgi, becomes extensively oxidized and converted into large aggregates. The aggregates slowly degrade by an autophagic process. None of the oxidized, aggregated material leaves cells, thereby preventing export of apoB-lipoproteins containing potentially toxic lipid peroxides. In summary, apoB secretory control via PERPP/autophagosomes is likely a key component of normal and pathologic regulation of plasma apoB levels, as well as a means for remarkably late-stage quality control of a secreted protein.
authors.affiliation: Departments of Medicine, Leon H. Charney Division of Cardiology, and Cell Biology and the Marc and Ruti Bell Vascular Biology and Disease Program, New York University School of Medicine, New York, NY 10016, USA.
authors.forename: Meihui
authors.initials: M
authors.lastname: Pan
authors.forename: Vatsala
authors.initials: V
authors.lastname: Maitin
authors.forename: Sajesh
authors.initials: S
authors.lastname: Parathath
authors.forename: Ursula
authors.initials: U
authors.lastname: Andreo
authors.forename: Sharron X
authors.initials: SX
authors.lastname: Lin
authors.forename: Carly
authors.initials: C
authors.lastname: St Germain
authors.forename: Zemin
authors.initials: Z
authors.lastname: Yao
authors.forename: Frederick R
authors.initials: FR
authors.lastname: Maxfield
authors.forename: Kevin Jon
authors.initials: KJ
authors.lastname: Williams
authors.forename: Edward A
authors.initials: EA
authors.lastname: Fisher
mesh_terms: D000818:Animals; D001055:Apolipoproteins B / Q000378:metabolism*; D001343:Autophagy; D002478:Cells, Cultured; D005231:Fatty Acids, Unsaturated / Q000378:metabolism; D022781:Hepatocytes / Q000166:cytology / Q000378:metabolism*; D010447:Peptide Hydrolases / Q000378:metabolism; D010588:Phagosomes / Q000378:metabolism; D021381:Protein Transport; D051381:Rats; D017382:Reactive Oxygen Species
chemical_list: D001055:Apolipoproteins B; D005231:Fatty Acids, Unsaturated; D017382:Reactive Oxygen Species; D010447:Peptide Hydrolases