title: Molecular basis of peroxisomal biogenesis disorders caused by defects in peroxisomal matrix protein import.
abstract: Peroxisomal biogenesis disorders (PBDs) represent a spectrum of autosomal recessive metabolic disorders that are collectively characterized by abnormal peroxisome assembly and impaired peroxisomal function. The importance of this ubiquitous organelle for human health is highlighted by the fact that PBDs are multisystemic disorders that often cause death in early infancy. Peroxisomes contribute to central metabolic pathways. Most enzymes in the peroxisomal matrix are linked to lipid metabolism and detoxification of reactive oxygen species. Proper assembly of peroxisomes and thus also import of their enzymes relies on specific peroxisomal biogenesis factors, so called peroxins with PEX being the gene acronym. To date, 13 PEX genes are known to cause PBDs when mutated. Studies of the cellular and molecular defects in cells derived from PBD patients have significantly contributed to the understanding of the functional role of the corresponding peroxins in peroxisome assembly. In this review, we discuss recent data derived from both human cell culture as well as model organisms like yeasts and present an overview on the molecular mechanism underlying peroxisomal biogenesis disorders with emphasis on disorders caused by defects in the peroxisomal matrix protein import machinery.
authors.affiliation: Abteilung fur Systembiochemie, Medizinische Fakultat der Ruhr-Universitat, Bochum, Germany.
authors.forename: Shirisha
authors.initials: S
authors.lastname: Nagotu
authors.forename: Vishal C
authors.initials: VC
authors.lastname: Kalel
authors.forename: Ralf
authors.initials: R
authors.lastname: Erdmann
authors.forename: Harald W
authors.initials: HW
authors.lastname: Platta
mesh_terms: D000818:Animals; D006801:Humans; D009154:Mutation; D018901:Peroxisomal Disorders / Q000235:genetics / Q000378:metabolism*; D000074437:Peroxisomal Targeting Signal 2 Receptor; D000074435:Peroxisome-Targeting Signal 1 Receptor; D020675:Peroxisomes / Q000378:metabolism*; D011485:Protein Binding; D011499:Protein Processing, Post-Translational; D021381:Protein Transport; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000378:metabolism
chemical_list: D000074437:Peroxisomal Targeting Signal 2 Receptor; D000074435:Peroxisome-Targeting Signal 1 Receptor; D018160:Receptors, Cytoplasmic and Nuclear