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Annual Review of Genetics 2000The segregation of metabolic functions within discrete organelles is a hallmark of eukaryotic cells. These compartments allow for the concentration of related metabolic... (Review)
Review
The segregation of metabolic functions within discrete organelles is a hallmark of eukaryotic cells. These compartments allow for the concentration of related metabolic functions, the separation of competing metabolic functions, and the formation of unique chemical microenvironments. However, such organization is not spontaneous and requires an array of genes that are dedicated to the assembly and maintenance of these structures. In this review we focus on the genetics of peroxisome biogenesis and on how defects in this process cause human disease.
Topics: Animals; Humans; Peroxisomes; Protein Transport; Proteins
PubMed: 11092841
DOI: 10.1146/annurev.genet.34.1.623 -
FEMS Yeast Research Nov 2003Peroxisomes are essential organelles in many eukaryotes. Until recently, the main focus of the investigations concerning these important organelles was to understand the... (Review)
Review
Peroxisomes are essential organelles in many eukaryotes. Until recently, the main focus of the investigations concerning these important organelles was to understand the biogenesis of the peroxisome (induction, proliferation and matrix protein import). However, when peroxisomes become redundant they are quickly degraded by highly selective processes known as pexophagy. The first molecular studies on pexophagy have indicated that this process shares many features with certain transport pathways to the vacuole (vacuolar protein sorting, autophagy, cytoplasm-to-vacuole targeting and endocytosis). Nevertheless, recent data demonstrate that in addition to common genes also unique genes are required for these transport processes. The main focus for the future should therefore be on identifying the unique determinants of pexophagy. Earlier results suggest that in the methylotrophic yeast Hansenula polymorpha proteins located on the peroxisome itself are required for pexophagy. Thus, it has become essential to study in detail the role of peroxisomal membrane proteins in the degradation process. This review highlights the main achievements of the last few years, with emphasis on H. polymorpha.
Topics: Biological Transport; Carrier Proteins; Cell Compartmentation; Fungal Proteins; Gene Expression Regulation, Fungal; Homeostasis; Membrane Proteins; Peroxisomes; Pichia
PubMed: 14613877
DOI: 10.1016/S1567-1356(03)00070-9 -
Plant Science : An International... Sep 2013Plant metabolic engineering is a promising tool for biotechnological applications. Major goals include enhancing plant fitness for an increased product yield and... (Review)
Review
Plant metabolic engineering is a promising tool for biotechnological applications. Major goals include enhancing plant fitness for an increased product yield and improving or introducing novel pathways to synthesize industrially relevant products. Plant peroxisomes are favorable targets for metabolic engineering, because they are involved in diverse functions, including primary and secondary metabolism, development, abiotic stress response, and pathogen defense. This review discusses targets for manipulating endogenous peroxisomal pathways, such as fatty acid β-oxidation, or introducing novel pathways, such as the synthesis of biodegradable polymers. Furthermore, strategies to bypass peroxisomal pathways for improved energy efficiency and detoxification of environmental pollutants are discussed. In sum, we highlight the biotechnological potential of plant peroxisomes and indicate future perspectives to exploit peroxisomes as biofactories.
Topics: Biomass; Biotechnology; Metabolic Networks and Pathways; Peroxisomes; Plant Immunity; Plant Proteins; Plants; Plants, Genetically Modified; Reactive Oxygen Species; Stress, Physiological
PubMed: 23849130
DOI: 10.1016/j.plantsci.2013.06.005 -
The International Journal of... Jun 2011Peroxisomes are ubiquitous organelles surrounded by a single membrane that display a variety of metabolic functions. These vary with the organism in which they occur and... (Review)
Review
Peroxisomes are ubiquitous organelles surrounded by a single membrane that display a variety of metabolic functions. These vary with the organism in which they occur and with environmental conditions. Peroxisomes multiply by division of existing organelles and can be formed from ER. The peroxisomal membrane, akin to the organelle itself, is a very dynamic structure that obtains building blocks from the ER. It can form diverse organized structures - lipid domains - that can be involved in regulation of various vesicle fusion processes. Additionally, this membrane may undergo extensive changes in lipid composition. We recently showed that upon proliferation the peroxisomal membrane changes its curvature in response to the activity of the peroxisomal membrane protein Pex11. Tubulation of the organelle may be important for efficient recruitment of GTPases from the dynamin protein family that is involved in organelle fission.
Topics: Animals; Cytoplasmic Vesicles; Endoplasmic Reticulum; GTP Phosphohydrolases; Humans; Intracellular Membranes; Lipid Metabolism; Membrane Proteins; Peroxisomal Disorders; Peroxisomes
PubMed: 21419861
DOI: 10.1016/j.biocel.2011.03.006 -
Cell Biochemistry and Biophysics 2000Peroxisome assembly in mammals requires more than 14 genes. So far, we have isolated seven complementation groups (CGs) of peroxisome biogenesis-defective Chinese... (Review)
Review
Peroxisome assembly in mammals requires more than 14 genes. So far, we have isolated seven complementation groups (CGs) of peroxisome biogenesis-defective Chinese hamster ovary (CHO) cell mutants, Z65, Z24/ZP107, ZP92, ZP105/ZP139, ZP109, ZP110, ZP114. Two peroxin cDNAs, PEX2 and PEX6, were first cloned by genetic phenotype-complementation assay using Z65 and ZP92, respectively, and were shown to be responsible for peroxisome biogenesis disorders (PBD) such as Zellweger syndrome, of CG-F (the same as CG-X in U.S.A.) and CG-C (the same as CG-IV), respectively. Pex2p is a RING zinc finger membrane protein of peroxisomes and Pex6p is a member of the AAA ATPase family. We likewise isolated PEX12 encoding a peroxisomal integral membrane protein in the RING family, by functional complementation of ZP109, demonstrating PEX12 to be responsible for CG-III PBD. We also cloned PEX1 by screening of human liver cDNA library, using ZP107. PEX1 mutation was delineated to be the genetic cause of PBD in the most highest incidence group, CG-E (the same as CG-I). Moreover, we recently found that Pex5p is involved in transport of not only PTS1- but also PTS2-protein, distinct from yeast Pex5p, using PEX5-defective ZP105 and ZP139. Thus, CHO cell mutants defective in peroxisome biogenesis are indeed shown to be very useful for the studies of peroxisome assembly and delineating pathogenic genes in PBD. Furthermore, we have isolated novel CGs of CHO mutants, ZP119 and ZP126.
Topics: Gene Expression Regulation; Humans; Membrane Proteins; Mutation; Peroxisomal Disorders; Peroxisomes
PubMed: 11330042
DOI: 10.1385/cbb:32:1-3:155 -
Advances in Experimental Medicine and... 2020Fourteen PEX genes are currently identified as genes responsible for peroxisome biogenesis disorders (PBDs). Patients with PBDs manifest as neurodegenerative symptoms... (Review)
Review
Fourteen PEX genes are currently identified as genes responsible for peroxisome biogenesis disorders (PBDs). Patients with PBDs manifest as neurodegenerative symptoms such as neuronal migration defect and malformation of the cerebellum. To address molecular mechanisms underlying the pathogenesis of PBDs, mouse models for the PBDs have been generated by targeted disruption of Pex genes. Pathological phenotypes and metabolic abnormalities in Pex-knockout mice well resemble those of the patients with PBDs. The mice with tissue- or cell type-specific inactivation of Pex genes have also been established by using a Cre-loxP system. The genetically modified mice reveal that pathological phenotypes of PBDs are mediated by interorgan and intercellular communications. Despite the illustrations of detailed pathological phenotypes in the mutant mice, mechanistic insights into pathogenesis of PBDs are still underway. In this chapter, we overview the phenotypes of Pex-inactivated mice and the current understanding of the pathogenesis underlying PBDs.
Topics: Animals; Disease Models, Animal; Humans; Mice; Peroxisomal Disorders; Peroxisomes; Phenotype
PubMed: 33417212
DOI: 10.1007/978-3-030-60204-8_10 -
Current Opinion in Cell Biology Feb 2009Peroxisomes are single-membraned organelles ubiquitous to eukaryotic cells that house metabolic reactions that generate and destroy harmful oxidative intermediates. They... (Review)
Review
Peroxisomes are single-membraned organelles ubiquitous to eukaryotic cells that house metabolic reactions that generate and destroy harmful oxidative intermediates. They are dynamic structures whose morphology, abundance, composition, and function depend on the cell type and environment. Perhaps due to the potentially damaging and protective metabolic roles of peroxisomes and their dynamic presence in the cell, peroxisome biogenesis is emerging as a process that involves complex underlying mechanisms of regulated formation and maintenance. There are roughly 30 known peroxins, proteins involved in peroxisome biogenesis, many of which have been conserved from yeast to mammals. This review focuses on the biogenesis of peroxisomes with an emphasis on the regulation of peroxisome formation and the import of peroxisomal matrix proteins in the model organism Saccharomyces cerevisiae.
Topics: Membrane Proteins; Models, Molecular; Peroxisomes; Saccharomyces cerevisiae
PubMed: 19188056
DOI: 10.1016/j.ceb.2009.01.009 -
Genes To Cells : Devoted To Molecular &... Nov 2021Peroxisomes are single membrane-bound organelles important for the optimum functioning of eukaryotic cells. Seminal discoveries in the field of peroxisomes are made... (Review)
Review
Peroxisomes are single membrane-bound organelles important for the optimum functioning of eukaryotic cells. Seminal discoveries in the field of peroxisomes are made using yeast as a model. Several proteins required for the biogenesis and function of peroxisomes are identified to date. As with proteins involved in other major cellular pathways, peroxisomal proteins are also subjected to regulatory post-translational modifications. Identification, characterization and mapping of these modifications to specific amino acid residues on proteins are critical toward understanding their functional significance. Several studies have tried to identify post-translational modifications of peroxisomal proteins and determine their impact on peroxisome structure and function. In this manuscript, we provide an overview of the various post-translational modifications that govern the peroxisome dynamics in yeast.
Topics: Peroxisomes; Protein Processing, Post-Translational; Proteins; Saccharomyces cerevisiae
PubMed: 34472666
DOI: 10.1111/gtc.12892 -
Cold Spring Harbor Perspectives in... May 2013Peroxisomes are essential cellular organelles involved in lipid metabolism. Patients affected by severe peroxisome biogenesis disorders rarely survive their first year.... (Review)
Review
Peroxisomes are essential cellular organelles involved in lipid metabolism. Patients affected by severe peroxisome biogenesis disorders rarely survive their first year. Genetic screens in several model organisms have identified more than 30 PEX genes that are required for the formation of functional peroxisomes. Despite significant work on the PEX genes, the biogenic origin of peroxisomes remains controversial. For at least two decades, the prevailing model postulated that peroxisomes propagate by growth and fission of preexisting peroxisomes. In this review, we focus on the recent evidence supporting a new, semiautonomous model of peroxisomal biogenesis. According to this model, peroxisomal membrane proteins (PMPs) traffic from the endoplasmic reticulum (ER) to the peroxisome by a vesicular budding, targeting, and fusion process while peroxisomal matrix proteins are imported into the organelle by an autonomous, posttranslational mechanism. We highlight the contradictory conclusions reached to answer the question of how PMPs are inserted into the ER. We then review what we know and what still remains to be elucidated about the mechanism of PMP exit from the ER and the contribution of preperoxisomal vesicles to mature peroxisomes. Finally, we discuss discrepancies in our understanding of de novo peroxisome biogenesis in wild-type cells. We anticipate that resolving these key issues will lead to a more complete picture of peroxisome biogenesis.
Topics: Endoplasmic Reticulum; Intracellular Membranes; Lipid Metabolism; Membrane Proteins; Peroxisomes; Protein Transport
PubMed: 23637287
DOI: 10.1101/cshperspect.a013243 -
Current Biology : CB Sep 2005The long-standing and thorny issue of the origin of peroxisomes has at last been solved. New evidence demonstrates conclusively that the peroxisomal membrane originates... (Review)
Review
The long-standing and thorny issue of the origin of peroxisomes has at last been solved. New evidence demonstrates conclusively that the peroxisomal membrane originates from the endoplasmic reticulum. This process requires the two peroxins Pex3p and Pex19p leading to intermediate structures that then mature into functionally competent organelles.
Topics: Endoplasmic Reticulum; Intracellular Membranes; Membrane Proteins; Models, Biological; Peroxisomes
PubMed: 16169481
DOI: 10.1016/j.cub.2005.08.056