The role of peroxisomes in the biosynthesis of isoprenoids including cholesterol has remained hotly disputed in the literature. We showed in a cell culture model that the biosynthesis of cholesterol from [1-14C]acetyl-CoA, which had been generated through peroxisomal ß-oxidation of a VLCFA ([1-14C]C24:0) substrate, is not inhibited by lovastatin. In contrast, the biosynthesis of cholesterol using either [1-14C]acetyl-CoA generated by mitochondrial ß-oxidation of a [1-14C]C8:0 substrate or a directly added [1-14C]acetyl-CoA (in both cases presumably occurring at the ER) is strongly inhibited.
Fig: Cholesterol biosynthesis from [1-14C]C24:0-derived acetyl-CoA is not impaired by statin treatment. Cos-7 cells were incubated with either [2-14C]acetate, [1-14C]C8:0 or [1-14C]C24:0 and treated with lovastatin or the solvent DMSO for 24 h. To assess cholesterol biosynthesis, lipids were extracted from cell lysates, separated by TLC and the radioactivity of the cholesterol fraction was quantified by liquid scintillation counting. Results were normalized to cellular protein content and to an internal [3H]cholesterol recovery standard. Data are shown as means ± SD with the number of analyzed samples in parentheses. Statistically significant differences (Student´s t-test) are indicated by asterisks (p < 0.05).
Click here to read more about the role of peroxisomes in cholesterol biosynthesis -pdf-
