Role of peroxisomes in sterol carrier protein 2 (SCP2) metabolism

Sterol carrier protein 2 (SCP2) is an intracellular protein that functions as a carrier for phospholipids and sterols in vitro. It is the product of a complex gene (SCP2/SCPX) that not only encodes the message for the 14kDa SCP2 protein but also translates a second larger gene product of 58 kDa, SCPX. Both SCP2 and SCPX contain a carboxy-terminal peroxisomal targeting signal l (PTS1) and have been localized to peroxisomes. Even though the SCP2/SCPX gene contains 2 alternative promoters and yields these 2 proteins m vitro, its is not clear if intraperoxisomal SCP2 arises from proteolytic degradation of the 58kDa SCPX or by direct import of SCP2 into peroxisomes in vivo. To address this question, we performed immunoblot and immunofluorescence studies in fibroblasts using antibody raised against SCP2. The 14kDa SCP2 but not the 5SkDa SCPX was detected on Western blots of control human fibroblasts; in contrast, cells from patients with peroxisomal biogenesis disorders (PBD) had a signal at 58kDa but no SCP2 was detectable. In indirect immunofluorescence studies of control fibroblasts, SCP2 signal colocalized in a punctate pattern with the peroxisome marker catalase, while in PBD patients' cells, the cytosol was diffusely stained with both SCP2 and catalase antibodies. These findings are consistent with the inability to import PTSl proteins in PBD patients and suggest that in fibroblasts SCP2 likely arises from proteolytic processing of SCP within peroxisomes.