SUPPRESSION OF PEROXISOMAL MEMBRANE-PROTEIN DEFECTS BY PEROXISOMAL ATP BINDING CASSETTE (ABC) PROTEINS

X-Linked adrenoleukodystrophy (X-ALD) is a neurodegenerative disorder characterized by reduced peroxisomal very long chain fatty acid (VLCFA ) beta-oxidation. The X-ALD gene product (ALDP) is a peroxisomal trans membrane protein with an ATP binding cassette (ABC), ALDP and three ot her ABC proteins (PMP70, ALDR, P70R) localize to the peroxisomal membr ane, The function of this family of peroxisomal membrane proteins is u nknown, We used complementation studies to begin analysis of their rol e in VLCFA beta-oxidation and on the peroxisomal membrane. Expression of either ALDP or PMP70 restores VLCFA beta-oxidation in X-ALD fibrobl asts, indicating overlapping functions, Their expression also restores peroxisome biogenesis in cells that are deficient in the peroxisomal membrane protein Pex2p, Thus it is likely that complex protein interac tions are involved in the function and biogenesis of peroxisomal membr anes that may contribute to disease heterogeneity.