Disease relevance of PEX6

• A PEX6-defective peroxisomal biogenesis disorder with severe phenotype in an infant, versus mild phenotype resembling Usher syndrome in the affected parents [1].
• Rhythm versus rate control after ablation and pacing for paroxysmal atrial fibrillation: clinical implications of the PAF 2 trial [2].

High impact information on PEX6

• Thus, Pex26 recruits Pex6-Pex1 complexes to peroxisomes [3].
• Epitope-tagged Pex6 and Pex1 are discernible as puncta in normal CHO-K1 cells, but not in PEX26-defective cells [3].
• We have identified the human gene PXAAA1 based upon its similarity to PpPAS5, a gene required for peroxisome assembly in the yeast Pichia pastoris [4].
• Expression of PXAAA1 restored peroxisomal protein import in fibroblasts from 16 unrelated members of complementation group 4 (CG4) of the PBD [4].
• To clarify the novel pathogenic gene of PBD, we cloned the full-length human PAF-2 cDNA that morphologically and biochemically restores peroxisomes of group C Zellweger fibroblasts (the same as group 4 in the Kennedy-Krieger Institute) and identified two pathogenic mutations in the PAF-2 gene in two patients with group C Zellweger syndrome [5].

Biological context of PEX6

• This mutation analysis will aid in understanding the functions of the PEX6 protein in peroxisomal biogenesis [6].
• The human PEX6 gene consists of 17 exons and 16 introns, spanning about 14kb [6].
• In addition, ZP92 transfected with G708D in PEX6, the counterpart to the temperature-sensitive mutation G843D in PEX1, revealed no temperature-sensitive phenotype [7].
• This patient was a compound heterozygote for PEX6 gene alleles [8].
• Peroxisomes were morphologically and biochemically formed at 30 degrees C but not at 37 degrees C. This patient was homozygous for a missense mutation, T-->C at nucleotide 170 resulting in a change from leucine to proline at amino acid 57 (L57P) in Pex6p [7].

Anatomical context of PEX6

• Temperature-sensitive mutation of PEX6 in peroxisome biogenesis disorders in complementation group C (CG-C): comparative study of PEX6 and PEX1 [7].
• Expression of PEX6 restored peroxisome assembly in fibroblasts from a CG6 PBD patient [8].
• We found PEX26-Mito localized to the mitochondria and directed all detectable PEX6 and a fraction of PEX1 to this extraperoxisomal location; yet PEX26-Mito retains the full ability to rescue peroxisome biogenesis in PEX26-deficient cells [9].
• Peroxisomes are formed from complex membrane structures in PEX6-deficient CHO cells upon genetic complementation [10].
• We demonstrate that Pex1p and Pex6p form a stable complex in the cytosol, which associates at the peroxisomal membrane with their membrane anchor Pex15p and the peroxisomal importomer [11].

Associations of PEX6 with chemical compounds

• Together with the requirement of PEX6 for appressorial melanization, our findings suggest that peroxisomal metabolic pathways play functional roles in appressorial melanization and subsequent host invasion steps, and the latter step requires the glyoxylate cycle [12].
• Electron microscopic analysis revealed restored peroxisomes in methanol-induced cold-sensitive pex6 cells at both permissive and restrictive temperatures [13].
• An unusual phenotype of the pex1 and pex6 mutants was that they grew poorly with glucose as the carbon source, but nearly wild type with galactose, which suggested impaired hexokinase function and that C. neoformans peroxisomes might function analogously to the glycosomes of the trypanosomid parasites [14].

Other interactions of PEX6

• The validity of this approach is demonstrated by its use in identifying PXR1 as the human orthologue of the Pichia pastoris PAS8 gene and PXAAA1 as a human homologue of the Pichia pastoris PAS5 gene [15].
• In the early stage of complementation by PEX6 cDNA, catalase and acyl-CoA oxidase accumulated in the lumen of the double-membraned loops [10].

References