Intramitochondrial localization and proposed metabolic significance of serine transhydroxymethylase

Abstract

Serine transhydroxymethylase is a latent enzyme of intact rat liver mitochondria. The enzyme is neither solubilized by the selective removal of the outer membrane with digitonin, nor inactivated by concentrations of diazobenzenesulfonate that do not penetrate the inner membrane, but that do inhibit solubilized serine transhydroxymethylase. Swelling of mitochondria was studied in isoosmotic solutions of substrates under conditions that would define transport as neutral uniport, anion-hydroxyl exchange, anion-anion exchange, or electrophoretic. L-Serine and glycine appear to be rapidly taken up by a nonelectrophoretic uniport mechanism, while folate and tetrahydrofolate are not tranported. The results localize the enzyme in the matrix and indicate that the latent activity results from a lack of tetrahydrofolate transport across the inner membrane. Based on these results, the dual localization of serine transhydroxymethylase in the mitochondria and the cytosol is proposed to provide a one-carbon shuttle system to link one-carbon metabolism in the two-cellular compartments.