CHARACTERIZATION OF UT2 CELLS - THE INDUCTION OF PEROXISOMAL 3-HYDROXY-3-METHYLGLUTARYL-COENZYME-A REDUCTASE

In the liver 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase is present not only in the endoplasmic reticulum but also in the pero xisomes, However, to date no information is available regarding the fu nction 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 e xpresses only one HMG-CoA reductase protein and that is localized excl usively to peroxisomes, This cell line was obtained by growing UT2 cel ls (which lack the en doplasmic reticulum HMG-CoA reductase) in the ab sence 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 pr oteins, the well characterized 97-kDa protein, localized in the endopl asmic reticulum, and a 90-kDa protein localized in peroxisomes. The UT 2 cells grown in the absence of mevalonate containing the up-regulated peroxisomal HMG-CoA reductase are designated UT2. A detailed charact erization and analysis of this cell line is presented in this study.