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Plant Physiology Nov 2001
Review
Topics: Carrier Proteins; Fungal Proteins; Heat-Shock Proteins; Intracellular Membranes; Membrane Proteins; Membrane Transport Proteins; Models, Biological; Molecular Chaperones; Peroxisomal Targeting Signal 2 Receptor; Peroxisome-Targeting Signal 1 Receptor; Peroxisomes; Receptors, Cytoplasmic and Nuclear; Repressor Proteins; Signal Transduction
PubMed: 11706158
DOI: No ID Found -
The Journal of Cell Biology Jul 2006Peroxisomes have long been viewed as semiautonomous, static, and homogenous organelles that exist outside the secretory and endocytic pathways of vesicular flow.... (Review)
Review
Peroxisomes have long been viewed as semiautonomous, static, and homogenous organelles that exist outside the secretory and endocytic pathways of vesicular flow. However, growing evidence supports the view that peroxisomes actually constitute a dynamic endomembrane system that originates from the endoplasmic reticulum. This review highlights the various strategies used by evolutionarily diverse organisms for coordinating the flow of membrane-enclosed carriers through the peroxisomal endomembrane system and critically evaluates the dynamics and molecular mechanisms of this multistep process.
Topics: Animals; Endoplasmic Reticulum; Humans; Intracellular Membranes; Membrane Proteins; Models, Biological; Peroxisomes
PubMed: 16801391
DOI: 10.1083/jcb.200604036 -
Biomedicine & Pharmacotherapy =... Nov 2021Ferroptosis is a recently recognized process of cell death characterized by accumulation of iron-dependent lipid peroxides. Herein, we demonstrate that peroxisome...
Ferroptosis is a recently recognized process of cell death characterized by accumulation of iron-dependent lipid peroxides. Herein, we demonstrate that peroxisome proliferator-activated receptor δ (PPARδ) inhibits ferroptosis of mouse embryonic fibroblasts (MEFs) derived from cysteine/glutamate transporter (xCT)-knockout mice. Activation of PPARδ by the specific ligand GW501516 led to a dose-dependent decrease in ferroptotic cell death triggered by xCT deficiency, along with decreased levels of intracellular iron accumulation and lipid peroxidation. These effects of GW501516 were abolished by PPARδ-targeting small interfering RNA (siRNA) and the PPARδ inhibitor GSK0660, indicating that PPARδ inhibits xCT deficiency-induced ferroptosis. In addition, GW501516-activated PPARδ time- and dose-dependently upregulated catalase expression at both the mRNA and protein levels. This PPARδ-mediated upregulation of catalase was markedly attenuated in cells treated with PPARδ-targeting siRNA and GSK0660, indicating that expression of catalase is dependent on PPARδ. Consistently, the effects of GW501516 on ferroptosis of xCT-deficient MEFs were counteracted in the presence of 3-amino-1,2,4-triazole, a specific inhibitor of catalase, suggesting that catalase is essential for the effect of PPARδ on ferroptosis triggered by xCT deficiency. GW501516-activated PPARδ stabilized peroxisomes through catalase upregulation by targeting peroxisomal hydrogen peroxide-mediated lysosomal rupture, which led to ferroptosis of xCT-deficient MEFs. Collectively, these results demonstrate that PPARδ modulates ferroptotic signals in xCT-deficient MEFs by regulating catalase expression.
Topics: Amino Acid Transport System y+; Animals; Catalase; Cells, Cultured; Enzyme Induction; Ferroptosis; Fibroblasts; Hydrogen Peroxide; Lipid Peroxidation; Mice, Knockout; Oxidative Stress; PPAR gamma; Peroxisomes; Signal Transduction; Thiazoles; Mice
PubMed: 34649350
DOI: 10.1016/j.biopha.2021.112223 -
Biochimica Et Biophysica Acta Sep 2012Human peroxisome biogenesis disorders (PBDs) are a heterogeneous group of autosomal recessive disorders comprised of two clinically distinct subtypes: the Zellweger... (Review)
Review
Human peroxisome biogenesis disorders (PBDs) are a heterogeneous group of autosomal recessive disorders comprised of two clinically distinct subtypes: the Zellweger syndrome spectrum (ZSS) disorders and rhizomelic chondrodysplasia punctata (RCDP) type 1. PBDs are caused by defects in any of at least 14 different PEX genes, which encode proteins involved in peroxisome assembly and proliferation. Thirteen of these genes are associated with ZSS disorders. The genetic heterogeneity among PBDs and the inability to predict from the biochemical and clinical phenotype of a patient with ZSS which of the currently known 13 PEX genes is defective, has fostered the development of different strategies to identify the causative gene defects. These include PEX cDNA transfection complementation assays followed by sequencing of the thus identified PEX genes, and a PEX gene screen in which the most frequently mutated exons of the different PEX genes are analyzed. The benefits of DNA testing for PBDs include carrier testing of relatives, early prenatal testing or preimplantation genetic diagnosis in families with a recurrence risk for ZSS disorders, and insight in genotype-phenotype correlations, which may eventually assist to improve patient management. In this review we describe the current status of genetic analysis and the molecular basis of PBDs.
Topics: ATPases Associated with Diverse Cellular Activities; Adenosine Triphosphatases; Female; Genetic Association Studies; Humans; Membrane Proteins; Molecular Diagnostic Techniques; Mutation; Peroxisomal Disorders; Peroxisomes; Pregnancy; Prenatal Diagnosis; Protein Transport
PubMed: 22871920
DOI: 10.1016/j.bbadis.2012.04.006 -
Molecular Genetics and Metabolism Oct 1999Genetically determined human peroxisomal disorders are subdivided into two major categories: disorders of peroxisome biogenesis (PBD), in which the organelle is not... (Review)
Review
Genetically determined human peroxisomal disorders are subdivided into two major categories: disorders of peroxisome biogenesis (PBD), in which the organelle is not formed normally, and those that involve a single peroxisomal enzyme. Twelve PBD have been identified, and the molecular defects have been defined in 10. All involve defects in the import of proteins into the organelle. Factors required for this import are now referred to as peroxins (PEX) and form the basis of a new and preferred classification system. The PBD are associated with four clinical phenotypes, named before their association with the organelle was recognized: Zellweger syndrome (ZS), neonatal adrenoleukodystrophy (NALD), infantile Refsum disease (IRD), and rhizomelic chondrodysplasia punctata (RCDP). The first three are associated with 9 of the 10 PEX defects that have been defined so far, and represent a clinical continuum with variant severity, with ZS the most severe, NALD intermediate, and IRD the least severe. RCDP is associated with PEX7. Genotype-phenotype correlations are complicated by the fact that the clinical manifestations of the ZS-NALD-IRD continuum can be mimicked by disorders that affect single enzymes of peroxisomal fatty acid oxidation, and PEX7 by disorders of plasmalogen synthesis enzymes. Furthermore, clinical manifestations of each of the PEX disorders may vary. Phenotypic expression varies with the nature of the mutation, the milder phenotypes being associated with mutations that do not abolish function completely, or with mosaicism. Definition of the molecular defects is of great value for genetic counseling and may be of aid in establishing prognosis.
Topics: Genotype; Humans; Mutation; Peroxisomal Disorders; Peroxisomes; Phenotype; Proteins
PubMed: 10527683
DOI: 10.1006/mgme.1999.2926 -
Tanpakushitsu Kakusan Koso. Protein,... May 2004
Review
Topics: ATPases Associated with Diverse Cellular Activities; Animals; CHO Cells; Cloning, Molecular; Cricetinae; Humans; Membrane Proteins; Peroxins; Peroxisomal Biogenesis Factor 2; Peroxisomal Disorders; Peroxisomal Targeting Signal 2 Receptor; Peroxisome-Targeting Signal 1 Receptor; Peroxisomes; Protein Transport; Receptors, Cytoplasmic and Nuclear; Signal Transduction
PubMed: 15168551
DOI: No ID Found -
Biochimica Et Biophysica Acta Dec 2006The perceived role of the ER in the biogenesis of plant peroxisomes has evolved significantly from the original "ER vesiculation" model, which portrayed co-translational... (Review)
Review
The perceived role of the ER in the biogenesis of plant peroxisomes has evolved significantly from the original "ER vesiculation" model, which portrayed co-translational import of proteins into peroxisomes originating from the ER, to the "ER semi-autonomous peroxisome" model wherein membrane lipids and post-translationally acquired peroxisomal membrane proteins (PMPs) were derived from the ER. Results from more recent studies of various plant PMPs including ascorbate peroxidase, PEX10 and PEX16, as well as a viral replication protein, have since led to the formulation of a more elaborate "ER semi-autonomous peroxisome maturation and replication" model. Herein we review these results in the context of this newly proposed model and its predecessor models. We discuss also key distinct features of the new model pertaining to its central premise that the ER defines the semi-autonomous maturation (maintenance/assembly/differentiation) and duplication (division) features of specialized classes of pre-existing plant peroxisomes. This model also includes a novel peroxisome-to-ER retrograde sorting pathway that may serve as a constitutive protein retrieval/regulatory system. In addition, new plant peroxisomes are envisaged to arise primarily by duplication of the pre-existing peroxisomes that receive essential membrane components from the ER.
Topics: Endoplasmic Reticulum; Models, Biological; Peroxisomes; Plants; Protein Transport
PubMed: 17049631
DOI: 10.1016/j.bbamcr.2006.09.011 -
Biochimica Et Biophysica Acta Jan 2012Peroxisome is a single-membrane organelle in eukaryotes. The functional importance of peroxisomes in humans is highlighted by peroxisome-deficient peroxisome biogenesis... (Review)
Review
New insights into dynamic and functional assembly of the AAA peroxins, Pex1p and Pex6p, and their membrane receptor Pex26p in shuttling of PTS1-receptor Pex5p during peroxisome biogenesis.
Peroxisome is a single-membrane organelle in eukaryotes. The functional importance of peroxisomes in humans is highlighted by peroxisome-deficient peroxisome biogenesis disorders such as Zellweger syndrome. Two AAA peroxins, Pex1p and Pex6p, are encoded by PEX1 and PEX6, the causal genes for PBDs of complementation groups 1 and 4, respectively. PEX26 responsible for peroxisome biogenesis disorders of complementation group 8 codes for C-tail-anchored type-II membrane peroxin Pex26p, the recruiter of Pex1p-Pex6p complexes to peroxisomes. Pex1p is targeted to peroxisomes in a manner dependent on ATP hydrolysis, while Pex6p targeting requires ATP but not its hydrolysis. Pex1p and Pex6p are most likely regulated in their peroxisomal localization onto Pex26p via conformational changes by ATPase cycle. Pex5p is the cytosolic receptor for peroxisome matrix proteins with peroxisome targeting signal type-1 and shuttles between the cytosol and peroxisomes. AAA peroxins are involved in the export from peroxisomes of Pex5p. Pex5p is ubiquitinated at the conserved cysteine11 in a form associated with peroxisomes. Pex5p with a mutation of the cysteine11 to alanine, termed Pex5p-C11A, abrogates peroxisomal import of proteins harboring peroxisome targeting signals 1 and 2 in wild-type cells. Pex5p-C11A is imported into peroxisomes but not exported, hence suggesting an essential role of the cysteine residue in the export of Pex5p.
Topics: ATPases Associated with Diverse Cellular Activities; Adenosine Triphosphatases; Amino Acid Sequence; Animals; Conserved Sequence; Humans; Membrane Proteins; Peroxisome-Targeting Signal 1 Receptor; Peroxisomes; Protein Multimerization; Protein Structure, Quaternary; Protein Structure, Tertiary; Protein Transport; Receptors, Cytoplasmic and Nuclear
PubMed: 22079764
DOI: 10.1016/j.bbamcr.2011.10.012 -
Biochimica Et Biophysica Acta.... Aug 2020Although obesity contributes to the onset and pathogenesis of metabolic diseases, it has been repeatedly demonstrated that being overweight or mildly obese carries a...
Although obesity contributes to the onset and pathogenesis of metabolic diseases, it has been repeatedly demonstrated that being overweight or mildly obese carries a survival advantage compared with being thin or normal-weight. This relationship is called the obesity paradox. Hence, it is necessary to clarify the underlying mechanism of obesity onset for the prevention and treatment of these diseases. Catalase is distributed in peroxisomes under normal redox conditions and catalase activity is increased during the differentiation of 3T3-L1 preadipocytes to adipocytes. Although peroxisomes are responsible for lipid metabolism, the role of peroxisomal catalase in the process of lipid accumulation remains unclear. The present study aimed to investigate the relationships among catalase activity, peroxisome content, and lipid accumulation during the differentiation of 3T3-L1 preadipocytes to adipocytes. Increased catalase activity and lipid accumulation were observed during the differentiation of preadipocytes. Silencing of catalase by small interfering RNA or treatment with 3-amino-1,2,4-triazole (3-AT), a catalase inhibitor, resulted in reduced lipid accumulation. Inhibition of catalase activity in peroxisomes increases hydrogen peroxide (HO) levels, which results in a reduction of peroxisome content. Extracellular HO had no influence on lipid accumulation during differentiation. The occurrence of autophagy was clearly enhanced in cells treated with 3-AT. Spautin-1, an inhibitor of autophagy flux, protected against a reduction in lipid accumulation by treatment with 3-AT. Our data provide evidence that catalase protects against the degradation of peroxisomes via the occurrence of autophagy triggered by the generation of HO in peroxisomes. These results suggest that catalase in peroxisomes is crucial to adipogenesis.
Topics: 3T3-L1 Cells; Adipocytes; Adipogenesis; Animals; Catalase; Cell Differentiation; Cells, Cultured; Mice; Peroxisomes
PubMed: 32335291
DOI: 10.1016/j.bbalip.2020.158726 -
Wei Sheng Wu Xue Bao = Acta... Dec 2008Peroxisome (P), a ubiquitous organelle in the eukaryotic cells, is involved in various important metabolic processes. Investigation of formation, proliferation and... (Review)
Review
Peroxisome (P), a ubiquitous organelle in the eukaryotic cells, is involved in various important metabolic processes. Investigation of formation, proliferation and degradation of the peroxisome is an important part of study of organelles biogenesis. So far, mechanism of the peroxisome biogenesis is not completely clear, although over 30 related genes were identified and characterized. Filamentous fungus, a multi-cellular eukaryotic organism containing many plant pathogens and economic species, holds great value of studying function and mechanism in the peroxisome biogenesis. The peroxisome researches have been progressed in recent years quickly after availability of the genome data and development of the fungal bio-techniques. Meanwhile greater interests have been demonstrated in area of the peroxisome biogenesis and in its roles of pathogenicity of several phytopathogenic fungi. The summary of mechanism of the peroxisome biogenesis in filamentous fungi and relationship between peroxisome and pathogenicity were reviewed in this paper
Topics: Biological Transport, Active; Fungi; Organelle Biogenesis; Peroxisomes; Plant Diseases; Saccharomyces cerevisiae
PubMed: 19271546
DOI: No ID Found