Abstract
In the liver 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase is present not only in the endoplasmic reticulum but also in the peroxisomes. However, to date no information is available regarding the function of the peroxisomal HMG-CoA reductase in cholesterol/isoprenoid metabolism, and the structure of the peroxisomal HMG-CoA reductase has yet to be determined. We have identified a mammalian cell line that expresses only one HMG-CoA reductase protein and that is localized exclusively to peroxisomes. This cell line was obtained by growing UT2 cells (which lack the endoplasmic reticulum HMG-CoA reductase) in the absence of mevalonate. The cells exhibited a marked increase in a 90-kDa HMG-CoA reductase that was localized exclusively to peroxisomes. The wild type Chinese hamster ovary cells contain two HMG-CoA reductase proteins, the well characterized 97-kDa protein, localized in the endoplasmic reticulum, and a 90-kDa protein localized in peroxisomes. The UT2 cells grown in the absence of mevalonate containing the up-regulated peroxisomal HMG-CoA reductase are designated UT2*. A detailed characterization and analysis of this cell line is presented in this study.
Highlights
In the liver 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase is present in the endoplasmic reticulum and in the peroxisomes
The wild type Chinese hamster ovary cells contain two HMG-CoA reductase proteins, the well characterized 97-kDa protein, localized in the endoplasmic reticulum, and a 90-kDa protein localized in peroxisomes
We have shown that CHO cells contain two reductase proteins, the well characterized 97-kDa protein, localized in the endoplasmic reticulum (ER) and a 90-kDa protein localized in peroxisomes
Summary
In the liver 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase is present in the endoplasmic reticulum and in the peroxisomes. The results clearly demonstrate that UT2* cells (panel A) express an HMG-CoA reductase that is both localized to the peroxisomes and is smaller in size than that observed in the ER (fractions 5– 8) of normal CHO cells (panel B).
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