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Biochimica Et Biophysica Acta Dec 2006The discovery of the colocalization of catalase with H2O2-generating oxidases in peroxisomes was the first indication of their involvement in the metabolism of oxygen... (Review)
Review
The discovery of the colocalization of catalase with H2O2-generating oxidases in peroxisomes was the first indication of their involvement in the metabolism of oxygen metabolites. In past decades it has been revealed that peroxisomes participate not only in the generation of reactive oxygen species (ROS) with grave consequences for cell fate such as malignant degeneration but also in cell rescue from the damaging effects of such radicals. In this review the role of peroxisomes in a variety of physiological and pathological processes involving ROS mainly in animal cells is presented. At the outset the enzymes generating and scavenging H2O2 and other oxygen metabolites are reviewed. The exposure of cultured cells to UV light and different oxidizing agents induces peroxisome proliferation with formation of tubular peroxisomes and apparent upregulation of PEX genes. Significant reduction of peroxisomal volume density and several of their enzymes is observed in inflammatory processes such as infections, ischemia-reperfusion injury and hepatic allograft rejection. The latter response is related to the suppressive effects of TNFalpha on peroxisomal function and on PPARalpha. Their massive proliferation induced by a variety of xenobiotics and the subsequent tumor formation in rodents is evidently due to an imbalance in the formation and scavenging of ROS, and is mediated by PPARalpha. In PEX5-/- mice with the absence of functional peroxisomes severe abnormalities of mitochondria in different organs are observed which resemble closely those in respiratory chain disorders associated with oxidative stress. Interestingly, no evidence of oxidative damage to proteins or lipids, nor of increased peroxide production has been found in that mouse model. In this respect the role of PPARalpha, which is highly activated in those mice, in prevention of oxidative stress deserves further investigation.
Topics: Animals; Catalase; Hydrogen Peroxide; Mice; Mice, Knockout; Mitochondria; Oxidative Stress; PPAR alpha; Peroxisome-Targeting Signal 1 Receptor; Peroxisomes; Reactive Oxygen Species; Receptors, Cytoplasmic and Nuclear
PubMed: 17034877
DOI: 10.1016/j.bbamcr.2006.09.006 -
FEMS Microbiology Reviews Jul 2000Peroxisomes are subcellular organelles and are present in virtually all eukaryotic cells. Characteristic features of these organelles are their inducibility and their... (Review)
Review
Peroxisomes are subcellular organelles and are present in virtually all eukaryotic cells. Characteristic features of these organelles are their inducibility and their functional versatility. Their importance in the intermediary metabolism of cells is exemplified by the discovery of several inborn, fatal peroxisomal errors in man, the so-called peroxisomal disorders. Recent findings in research on peroxisome biogenesis and function have demonstrated that peroxisomal matrix proteins and peroxisomal membrane proteins (PMPs) follow separate pathways to reach their target organelle. This paper addresses the principles of PMP sorting and summarizes the current knowledge of the role of these proteins in organelle biogenesis and function.
Topics: Animals; Humans; Membrane Proteins; Peroxisomes; Protein Processing, Post-Translational
PubMed: 10841974
DOI: 10.1111/j.1574-6976.2000.tb00543.x -
Biochimica Et Biophysica Acta Dec 2006Peroxisomes play an important role in the biosynthesis of bile acids because a peroxisomal beta-oxidation step is required for the formation of the mature C24-bile acids... (Review)
Review
Peroxisomes play an important role in the biosynthesis of bile acids because a peroxisomal beta-oxidation step is required for the formation of the mature C24-bile acids from C27-bile acid intermediates. In addition, de novo synthesized bile acids are conjugated within the peroxisome. In this review, we describe the current state of knowledge about all aspects of peroxisomal function in bile acid biosynthesis in health and disease. The peroxisomal enzymes involved in the synthesis of bile acids have been identified, and the metabolic and pathologic consequences of a deficiency of one of these enzymes are discussed, including the potential role of nuclear receptors therein.
Topics: Animals; Bile Acids and Salts; Disease Models, Animal; Humans; Mice; Mice, Knockout; Oxidation-Reduction; Peroxisomal Disorders; Peroxisomes
PubMed: 17034878
DOI: 10.1016/j.bbamcr.2006.09.001 -
Biochimica Et Biophysica Acta May 2016The correct topogenesis of peroxisomal membrane proteins is a crucial step for the formation of functioning peroxisomes. Although this process has been widely studied,... (Review)
Review
The correct topogenesis of peroxisomal membrane proteins is a crucial step for the formation of functioning peroxisomes. Although this process has been widely studied, the exact mechanism with which it occurs has not yet been fully characterized. Nevertheless, it is generally accepted that peroxisomes employ three proteins - Pex3, Pex19 and Pex16 in mammals - for the insertion of peroxisomal membrane proteins into the peroxisomal membrane. Structural biology approaches have been utilized for the elucidation of the mechanistic questions of peroxisome biogenesis, mainly by providing information on the architecture of the proteins significant for this process. This review aims to summarize, compare and put into perspective the structural knowledge that has been generated mainly for Pex3 and Pex19 and their interaction partners in recent years.
Topics: Animals; Eukaryotic Cells; Gene Expression Regulation; Humans; Membrane Proteins; Models, Molecular; Peroxins; Peroxisomes; Plants; Protein Isoforms; Protein Structure, Secondary; Protein Structure, Tertiary; Protein Transport; Saccharomyces cerevisiae; Saccharomyces cerevisiae Proteins; Signal Transduction
PubMed: 26434995
DOI: 10.1016/j.bbamcr.2015.09.031 -
Biochimica Et Biophysica Acta May 2016In the field of intracellular protein sorting, peroxisomes are most famous by their capacity to import oligomeric proteins. The data supporting this remarkable property... (Review)
Review
In the field of intracellular protein sorting, peroxisomes are most famous by their capacity to import oligomeric proteins. The data supporting this remarkable property are abundant and, understandably, have inspired a variety of hypothetical models on how newly synthesized (cytosolic) proteins reach the peroxisome matrix. However, there is also accumulating evidence suggesting that many peroxisomal oligomeric proteins actually arrive at the peroxisome still as monomers. In support of this idea, recent data suggest that PEX5, the shuttling receptor for peroxisomal matrix proteins, is also a chaperone/holdase, binding newly synthesized peroxisomal proteins in the cytosol and blocking their oligomerization. Here we review the data behind these two different perspectives and discuss their mechanistic implications on this protein sorting pathway.
Topics: Animals; Eukaryotic Cells; Gene Expression Regulation; Humans; Peroxisomal Targeting Signal 2 Receptor; Peroxisome-Targeting Signal 1 Receptor; Peroxisomes; Plants; Protein Isoforms; Protein Multimerization; Protein Structure, Secondary; Protein Structure, Tertiary; Protein Transport; Receptors, Cytoplasmic and Nuclear; Saccharomyces cerevisiae; Signal Transduction; Time Factors
PubMed: 26408939
DOI: 10.1016/j.bbamcr.2015.09.025 -
Traffic (Copenhagen, Denmark) Oct 2018The peroxisome matrix protein importomer has the remarkable ability to transport oligomeric protein substrates across the bilayer. However, the selectivity and relation...
The peroxisome matrix protein importomer has the remarkable ability to transport oligomeric protein substrates across the bilayer. However, the selectivity and relation between import and overall peroxisome homeostasis remain unclear. Here, we microinject artificial import substrates and employ quantitative microscopy to probe limits and capabilities of the importomer. DNA and polysaccharides are "piggyback" imported when noncovalently bound by a peroxisome targeting signal (PTS)-bearing protein. A dimerization domain that can be tuned to systematically vary the binding dissociation constant (K ) shows that a K in the millimolar range is sufficient to promote piggyback import. Microinjection of import substrate at high levels results in peroxisome growth and a proportional accumulation of peroxisome membrane proteins (PMPs). However, corresponding PMP mRNAs do not accumulate, suggesting that this response is posttranscriptionally regulated. Together, our data show that the importomer can tolerate diverse macromolecular species. Coupling between matrix import and membrane biogenesis suggests that matrix protein expression levels can be sufficient to regulate peroxisome size.
Topics: Animals; Cell Line; DNA; Escherichia coli; Intracellular Membranes; Luminescent Proteins; Membrane Proteins; Peroxisomal Targeting Signals; Peroxisome Proliferator-Activated Receptors; Peroxisomes; Polysaccharides; Protein Binding; Protein Multimerization; Protein Transport; Rats; Red Fluorescent Protein
PubMed: 30058098
DOI: 10.1111/tra.12607 -
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 -
Biochimica Et Biophysica Acta Mar 2011Peroxisomes are a class of structurally and functionally related organelles present in almost all eukaryotic cells. The importance of peroxisomes for human life is... (Review)
Review
Peroxisomes are a class of structurally and functionally related organelles present in almost all eukaryotic cells. The importance of peroxisomes for human life is highlighted by severe inherited diseases which are caused by defects of peroxins, encoded by PEX genes. To date 32 peroxins are known to be involved in different aspects of peroxisome biogenesis. This review addresses two of these aspects, the translocation of soluble proteins into the peroxisomal matrix and the biogenesis of the peroxisomal membrane. This article is part of a Special Issue entitled Protein translocation across or insertion into membranes.
Topics: Humans; Intracellular Membranes; Membrane Proteins; Peroxisomes; Protein Transport
PubMed: 20659419
DOI: 10.1016/j.bbamem.2010.07.020 -
International Journal of Molecular... Feb 2021The peroxisome is a single-membrane subcellular compartment present in almost all eukaryotic cells from simple protists and fungi to complex organisms such as higher... (Review)
Review
The peroxisome is a single-membrane subcellular compartment present in almost all eukaryotic cells from simple protists and fungi to complex organisms such as higher plants and animals. Historically, the name of the peroxisome came from a subcellular structure that contained high levels of hydrogen peroxide (HO) and the antioxidant enzyme catalase, which indicated that this organelle had basically an oxidative metabolism. During the last 20 years, it has been shown that plant peroxisomes also contain nitric oxide (NO), a radical molecule than leads to a family of derived molecules designated as reactive nitrogen species (RNS). These reactive species can mediate post-translational modifications (PTMs) of proteins, such as -nitrosation and tyrosine nitration, thus affecting their function. This review aims to provide a comprehensive overview of how NO could affect peroxisomal metabolism and its internal protein-protein interactions (PPIs). Remarkably, many of the identified NO-target proteins in plant peroxisomes are involved in the metabolism of reactive oxygen species (ROS), either in its generation or its scavenging. Therefore, it is proposed that NO is a molecule with signaling properties with the capacity to modulate the peroxisomal protein-protein network and consequently the peroxisomal functions, especially under adverse environmental conditions.
Topics: Nitric Oxide; Oxidation-Reduction; Peroxisomes; Plant Proteins; Plants; Protein Interaction Maps; Protein Processing, Post-Translational; Reactive Oxygen Species; Signal Transduction
PubMed: 33671021
DOI: 10.3390/ijms22052444 -
Biochimica Et Biophysica Acta Dec 2006Cells with a genetic defect affecting a biological activity and/or a cell phenotype are generally called "cell mutants" and are a highly useful tool in genetic,... (Review)
Review
Cells with a genetic defect affecting a biological activity and/or a cell phenotype are generally called "cell mutants" and are a highly useful tool in genetic, biochemical, as well as cell biological research. To investigate peroxisome biogenesis and human peroxisome biogenesis disorders, more than a dozen complementation groups of Chinese hamster ovary (CHO) cell mutants defective in peroxisome assembly have been successfully isolated and established as a model system. Moreover, successful PEX gene cloning studies by taking advantage of rapid functional complementation assay of CHO cell mutants invaluably contributed to the accomplishment of isolation of pathogenic genes responsible for peroxisome biogenesis diseases. Molecular mechanisms of peroxisome assembly are currently investigated by making use of such mammalian cell mutants.
Topics: Animals; CHO Cells; Cricetinae; Cricetulus; Mutation; Peroxisomes
PubMed: 17045664
DOI: 10.1016/j.bbamcr.2006.09.012