Increase in membrane cholesterol: A possible trigger for degradation of HMG CoA reductase and crystalloid endoplasmic reticulum in UT-1 cells

Lelio Orci, Michael S. Brown, Joseph L. Goldstein, Luis M. Garcia-Segura, Richard G W Anderson

Research output: Contribution to journalArticlepeer-review

65 Scopus citations

Abstract

The crystalloid endoplasmic reticulum (ER) houses large amounts of HMG CoA reductase, the rate-controlling enzyme in cholesterol synthesis. The crystalloid ER appears in UT-1 cells, a line of Chinese hamster ovary cells that has been chronically starved of cholesterol as a result of growth in the presence of compactin, an inhibitor of reductase. When cholesterol was provided to UT-1 cells in the form of low density lipoprotein (LDL), the reductase and crystalloid ER were destroyed. This destruction was preceded by an increase in the cholesterol content of crystalloid ER membranes, as judged by a 4- to 8-fold increase in their ability to form complexes with filipin, a cholesterol-binding compound that can be visualized in freeze-fracture electron micrographs. Filipin binding to other membranes was unchanged. Thus insertion of cholesterol into the crystalloid ER membrane may trigger the degradation of reductase and the membrane itself.

Original languageEnglish (US)
Pages (from-to)835-845
Number of pages11
JournalCell
Volume36
Issue number4
DOIs
StatePublished - Apr 1984

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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