The 22-kD Peroxisomal Integral Membrane Protein in Zellweger Syndrome—Presence, Abundance, and Association with a Peroxisomal Thiolase Precursor Protein

Abstract

ABSTRACT. The primary genetic defect of Zellweger syndrome may be related to defective synthesis or impaired import of peroxisomal proteins. We analyzed the presence and measured the abundance of the 22-kD peroxisomal integral membrane protein (PMP) in patients with Zellweger syndrome. We determined the intracellular localization of the 22-kD PMP and compared it with the localization of a peroxisomal 44-kD thiolase precursor protein.The 22-kD P M P was quantified by immunoblot analyses in liver tissue (n = 7 patients). Immunoblot signals were evaluated using transmission photometry. The intracellular localization of the 22-kD P M P and the peroxisomal 44-kD thiolase precursor protein were determined by immunoblot analyses on fibroblast subcellular fractions prepared by Nycodenz (n = 5 patients) or sucrose density gradient centrifugation (n = 2 patients). The 22-kD P M P was present and associated with membrane fractions in all patients. Its abundance varied in patients as compared with normal human liver controls. The 22-kD P M P was located in subcellular membrane fractions having a lower density than normal peroxisomes or mitochondria. Using two different gradient techniques, the 22-kD P M P and the peroxisomal 44-kD thiolase precursor protein were found in the same low-density gradient fractions. These results suggest that in Zellweger syndrome peroxisome-like elements containing both the 22-kD P M P and a 44-kD thiolase precursor protein are formed.

Reevaluation of the role of Pex1 and dynamin-related proteins in peroxisome membrane biogenesis

“…7). The shift to lower density fractions of peroxisomal membranes (ghosts) has been reported before (Santos et al, 1988;Gärtner et al, 1991;van Roermund et al, 1991;Motley et al, 1994;Hettema et al, 2000). Furthermore, differential centrifugation experiments (Fig.…”

Peroxisomal Lipid Metabolism

“…the �-oxidation enzymes) appear to be rapidly degraded in the cytosol. Interestingly, seemingly empty vesicular structures that contain some but not all of the peroxisomal integral membrane proteins and that may also contain the unprocessed thiolase precursor are found in the tissues of some Zellweger patients (19,82). The presence of these "peroxisomal ghosts" sug gests that more than one import route may exist and that not necessarily all routes are defective in peroxisome deficiency disorders.…”

Differential protein import deficiencies in human peroxisome assembly disorders.

“…Several investigations have indicated that peroxisomal ghosts fractionate at a lower density than peroxisomes from control cells (Santos et al, 1988;Gartner et al, 1991;Van Roermund et al, 1991). Subcellular fractionation was performed to investigate whether the prethiolase-containing particles in group IV cells also fractionate at a lower density than peroxisomes from control cells.…”