Presecretory oxidation, aggregation, and autophagic destruction of apoprotein-B: A pathway for late-stage quality control Academic Article uri icon

Overview

MeSH Major

  • Apolipoproteins B
  • Autophagy
  • Hepatocytes

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.

publication date

  • April 15, 2008

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed Central ID

  • PMC2311371

Digital Object Identifier (DOI)

  • 10.1073/pnas.0707460104

PubMed ID

  • 18391222

Additional Document Info

start page

  • 5862

end page

  • 7

volume

  • 105

number

  • 15