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Biological & Pharmaceutical Bulletin 2019Peroxisomes are indispensable organelles in mammals including humans. They are involved in the β-oxidation of very long chain fatty acids, and the synthesis of ether... (Review)
Review
Peroxisomes are indispensable organelles in mammals including humans. They are involved in the β-oxidation of very long chain fatty acids, and the synthesis of ether phospholipids and bile acids. Pre-peroxisomes bud from endoplasmic reticulum and peroxisomal membrane and matrix proteins are imported to the pre-peroxisomes. Then, matured peroxisomes grow by division. Impairment of the biogenesis and function of peroxisomes results in severe diseases. Since I first undertook peroxisome research in Prof. de Duve's laboratory at Rockefeller University in 1985, I have continuously studied peroxisomes for more than 30 years, with a particular focus on the ATP-binding cassette (ABC) transporters. Here, I review the history of peroxisome research, the biogenesis and function of peroxisomes, and peroxisome disease including X-linked adrenoleukodystrophy. The review includes the targeting and function of the ABC transporter subfamily D.
Topics: ATP-Binding Cassette Transporters; Adrenoleukodystrophy; Animals; Humans; Peroxisomes
PubMed: 31061307
DOI: 10.1248/bpb.b18-00723 -
Biological Chemistry Feb 2023
Topics: Endoplasmic Reticulum; Peroxisomes; Protein Transport
PubMed: 36597785
DOI: 10.1515/hsz-2022-0344 -
Biochimica Et Biophysica Acta May 2016Peroxisomal protein import is essentially different to the translocation of proteins into other organelles. The molecular mechanisms by which completely folded or even... (Review)
Review
Peroxisomal protein import is essentially different to the translocation of proteins into other organelles. The molecular mechanisms by which completely folded or even oligomerized proteins cross the peroxisomal membrane remain to be disclosed. The identification of a water-filled pore that is mainly constituted by Pex5 and Pex14 led to the assumption that proteins are translocated through a large, probably transient, protein-conducting channel. Here, we will review the work that led to the identification of this translocation pore. In addition, we will discuss the main biophysical features of the pore and compare it with other protein–translocation channels.
Topics: Animals; Eukaryotic Cells; Gene Expression Regulation; Humans; Peroxisomal Targeting Signal 2 Receptor; Peroxisome-Targeting Signal 1 Receptor; Peroxisomes; Plant Proteins; Plants; Protein Isoforms; Protein Sorting Signals; Protein Structure, Secondary; Protein Structure, Tertiary; Protein Transport; Receptors, Cytoplasmic and Nuclear; Saccharomyces cerevisiae; Signal Transduction
PubMed: 26497277
DOI: 10.1016/j.bbamcr.2015.10.013 -
Biochimica Et Biophysica Acta May 2016Our knowledge of the proteome of plant peroxisomes and their functional plasticity is far from being complete, primarily due to major technical challenges in... (Review)
Review
Our knowledge of the proteome of plant peroxisomes and their functional plasticity is far from being complete, primarily due to major technical challenges in experimental proteome research of the fragile cell organelle. Several unexpected novel plant peroxisome functions, for instance in biotin and phylloquinone biosynthesis, have been uncovered recently. Nevertheless, very few regulatory and membrane proteins of plant peroxisomes have been identified and functionally described up to now. To define the matrix proteome of plant peroxisomes, computational methods have emerged as important powerful tools. Novel prediction approaches of high sensitivity and specificity have been developed for peroxisome targeting signals type 1 (PTS1) and have been validated by in vivo subcellular targeting analyses and thermodynamic binding studies with the cytosolic receptor, PEX5. Accordingly, the algorithms allow the correct prediction of many novel peroxisome-targeted proteins from plant genome sequences and the discovery of additional organelle functions. In this review, we provide an overview of methodologies, capabilities and accuracies of available prediction algorithms for PTS1 carrying proteins. We also summarize and discuss recent quantitative, structural and mechanistic information of the interaction of PEX5 with PTS1 carrying proteins in relation to in vivo import efficiency. With this knowledge, we develop a model of how proteins likely evolved peroxisomal targeting signals in the past and still nowadays, in which order the two import pathways might have evolved in the ancient eukaryotic cell, and how the secondary loss of the PTS2 pathway probably happened in specific organismal groups.
Topics: Arabidopsis; Evolution, Molecular; Gene Expression Regulation, Plant; Onions; Peroxisomal Targeting Signal 2 Receptor; Peroxisome-Targeting Signal 1 Receptor; Peroxisomes; Plant Proteins; Protein Sorting Signals; Protein Transport; Receptors, Cytoplasmic and Nuclear; Signal Transduction; Nicotiana
PubMed: 26772785
DOI: 10.1016/j.bbamcr.2016.01.001 -
Biochimica Et Biophysica Acta May 2016Peroxisomes are dynamic, vital organelles that sequester a variety of oxidative reactions and their toxic byproducts from the remainder of the cell. The oxidative nature... (Review)
Review
Peroxisomes are dynamic, vital organelles that sequester a variety of oxidative reactions and their toxic byproducts from the remainder of the cell. The oxidative nature of peroxisomal metabolism predisposes the organelle to self-inflicted damage, highlighting the need for a mechanism to dispose of damaged peroxisomes. In addition, the metabolic requirements of plant peroxisomes change during development, and obsolete peroxisomal proteins are degraded. Although pexophagy, the selective autophagy of peroxisomes, is an obvious mechanism for executing such degradation, pexophagy has only recently been described in plants. Several recent studies in the reference plant Arabidopsis thaliana implicate pexophagy in the turnover of peroxisomal proteins, both for quality control and during functional transitions of peroxisomal content. In this review, we describe our current understanding of the occurrence, roles, and mechanisms of pexophagy in plants.
Topics: ATP-Dependent Proteases; Arabidopsis; Arabidopsis Proteins; Autophagy; Endoplasmic Reticulum; Gene Expression Regulation, Plant; Oxidation-Reduction; Peroxisomal Targeting Signal 2 Receptor; Peroxisome-Targeting Signal 1 Receptor; Peroxisomes; Protein Isoforms; Proteolysis; Receptors, Cytoplasmic and Nuclear; Signal Transduction; Ubiquitination
PubMed: 26348128
DOI: 10.1016/j.bbamcr.2015.09.005 -
Molecular Plant Pathology Jun 2022Several filamentous fungi are ecologically and economically important plant pathogens that infect a broad variety of crops. They cause high annual yield losses and... (Review)
Review
Several filamentous fungi are ecologically and economically important plant pathogens that infect a broad variety of crops. They cause high annual yield losses and contaminate seeds and fruits with mycotoxins. Not only powerful infection structures and detrimental toxins, but also cell organelles, such as peroxisomes, play important roles in plant infection. In this review, we summarize recent research results that revealed novel peroxisomal functions of filamentous fungi and highlight the importance of peroxisomes for infection of host plants. Central for fungal virulence are two primary metabolic pathways, fatty acid β-oxidation and the glyoxylate cycle, both of which are required to produce energy, acetyl-CoA, and carbohydrates. These are ultimately needed for the synthesis of cell wall polymers and for turgor generation in infection structures. Most novel results stem from different routes of secondary metabolism and demonstrate that peroxisomes produce important precursors and house various enzymes needed for toxin production and melanization of appressoria. All these peroxisomal functions in fungal virulence might represent elegant targets for improved crop protection.
Topics: Fungi; Peroxisomes; Plants; Virulence
PubMed: 35001508
DOI: 10.1111/mpp.13180 -
Biochimica Et Biophysica Acta Sep 2012Peroxisomes carry out many essential lipid metabolic functions. Nearly all of these functions require that an acyl group-either a fatty acid or the acyl side chain of a... (Review)
Review
Peroxisomes carry out many essential lipid metabolic functions. Nearly all of these functions require that an acyl group-either a fatty acid or the acyl side chain of a steroid derivative-be thioesterified to coenzyme A (CoA) for subsequent reactions to proceed. This thioesterification, or "activation", reaction, catalyzed by enzymes belonging to the acyl-CoA synthetase family, is thus central to cellular lipid metabolism. However, despite our rather thorough understanding of peroxisomal metabolic pathways, surprisingly little is known about the specific peroxisomal acyl-CoA synthetases that participate in these pathways. Of the 26 acyl-CoA synthetases encoded by the human and mouse genomes, only a few have been reported to be peroxisomal, including ACSL4, SLC27A2, and SLC27A4. In this review, we briefly describe the primary peroxisomal lipid metabolic pathways in which fatty acyl-CoAs participate. Then, we examine the evidence for presence and functions of acyl-CoA synthetases in peroxisomes, much of which was obtained before the existence of multiple acyl-CoA synthetase isoenzymes was known. Finally, we discuss the role(s) of peroxisome-specific acyl-CoA synthetase isoforms in lipid metabolism.
Topics: Acyl Coenzyme A; Amino Acid Sequence; Animals; Coenzyme A Ligases; Conserved Sequence; Fatty Acids; Humans; Lipid Metabolism; Molecular Sequence Data; Oxidation-Reduction; Peroxisomal Disorders; Peroxisomes
PubMed: 22366061
DOI: 10.1016/j.bbadis.2012.02.010 -
Current Opinion in Cell Biology Aug 2012Peroxisomes are essential organelles responsible for many metabolic reactions, such as the oxidation of very long chain and branched fatty acids, D-amino acids and... (Review)
Review
Peroxisomes are essential organelles responsible for many metabolic reactions, such as the oxidation of very long chain and branched fatty acids, D-amino acids and polyamines, as well as the production and turnover of hydrogen peroxide. They comprise a class of organelles called microbodies, including glycosomes, glyoxysomes and Woronin bodies. Dysfunction of human peroxisomes causes severe and often fatal peroxisome biogenesis disorders (PBDs). Peroxisomal matrix protein import is mediated by receptors that shuttle between the cytosol and peroxisomal matrix using ubiquitination/deubiquitination reactions and ATP hydrolysis for receptor recycling. We focus on the machinery involved in the peroxisomal matrix protein import cycle, highlighting recent advances in peroxisomal matrix protein import, cargo release and receptor recycling/degradation.
Topics: Cytosol; Glyoxysomes; Humans; Intracellular Membranes; Peroxisomes; Protein Sorting Signals; Protein Transport; Proteins; Ubiquitination
PubMed: 22683191
DOI: 10.1016/j.ceb.2012.05.003 -
Proceedings of the National Academy of... Jan 2020The adaptation of eukaryotic cells to anaerobic conditions is reflected by substantial changes to mitochondrial metabolism and functional reduction. Hydrogenosomes...
The adaptation of eukaryotic cells to anaerobic conditions is reflected by substantial changes to mitochondrial metabolism and functional reduction. Hydrogenosomes belong among the most modified mitochondrial derivative and generate molecular hydrogen concomitant with ATP synthesis. The reduction of mitochondria is frequently associated with loss of peroxisomes, which compartmentalize pathways that generate reactive oxygen species (ROS) and thus protect against cellular damage. The biogenesis and function of peroxisomes are tightly coupled with mitochondria. These organelles share fission machinery components, oxidative metabolism pathways, ROS scavenging activities, and some metabolites. The loss of peroxisomes in eukaryotes with reduced mitochondria is thus not unexpected. Surprisingly, we identified peroxisomes in the anaerobic, hydrogenosome-bearing protist We found a conserved set of peroxin (Pex) proteins that are required for protein import, peroxisomal growth, and division. Key membrane-associated Pexs (Pex3, Pex11, and Pex14) were visualized in numerous vesicles distinct from hydrogenosomes, the endoplasmic reticulum (ER), and Golgi complex. Proteomic analysis of cellular fractions and prediction of peroxisomal targeting signals (PTS1/PTS2) identified 51 putative peroxisomal matrix proteins. Expression of selected proteins in revealed specific targeting to peroxisomes. The matrix proteins identified included components of acyl-CoA and carbohydrate metabolism and pyrimidine and CoA biosynthesis, whereas no components related to either β-oxidation or catalase were present. In conclusion, we identified a subclass of peroxisomes, named "anaerobic" peroxisomes that shift the current paradigm and turn attention to the reductive evolution of peroxisomes in anaerobic organisms.
Topics: Anaerobiosis; Archamoebae; Mitochondria; Oxidation-Reduction; Peroxins; Peroxisomes; Protozoan Proteins; Reactive Oxygen Species
PubMed: 31932444
DOI: 10.1073/pnas.1909755117 -
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