Peroxisome Biogenesis Disorders

Abstract Peroxisome biogenesis disorders (PBDs) are autosomal recessive, progressive disorders characterised by loss of multiple peroxisomal metabolic functions and defects in peroxisome assembly, consisting of 13 complementation groups (CGs). Two mutually distinct but complementary approaches, forward genetic approach using more than a dozen CGs of peroxisome‐deficient Chinese hamster ovary (CHO) cell mutants and the homology search by screening the human expressed sequence tag (EST) database using yeast peroxin ( PEX ) genes, have been taken in order to isolate mammalian PEX genes. Search for pathogenic genes responsible for PBDs of all 13 CGs is now accomplished. Prenatal DNA diagnosis using PEX genes is now possible for PBDs of all 13 CGs. Moreover, molecular mechanisms underlying peroxisome biogenesis involving membrane assembly and matrix protein import are currently investigated by making use of PEX genes and pex cell mutants. Key Concepts: A single cell comprises more than a dozen different organelles that have unique protein compositions. Mechanisms underlying when and how these proteins are transported should be defined. The ways how the diverse sequences of proteins are recognised for translocation by the transport systems/machineries need to be delineated. The proteins and the lipid environment catalysing the protein transport must be addressed. Furthermore, during the cell cycle, each organelle must double in size, divide, and be delivered to its proper location in the daughter cells. How such events are accomplished and regulated should be defined. In tackling such issues, genetic phenotype complementation screening using mammalian somatic cell mutants and by taking advantage of highly sensitive and rapid detection may lead to cloning of genes essential for protein trafficking and organelle assembly. Mutations in genes are permanent alterations that may lead to changes in phenotype. Cell mutants are a highly useful tool in genetic, biochemical, as well as cell biological research. Several methods including the most recent lipofection have been developed for transfecting DNA into animal cells. Peroxisome biogenesis disorders (PBDs) are autosomal recessive, progressive disorders characterised by loss of multiple peroxisomal metabolic functions and defects in peroxisome assembly, consisting of more than a dozen complementation groups. Genetic phenotype‐complementation of peroxisome assembly‐defective mutants of mammalian somatic cells such as Chinese hamster ovary (CHO) cells and of several yeast species including Saccharomyces cerevisiae and Pichia pastoris would lead to identification and characterisation of numerous genes that are essential for peroxisome biogenesis.