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Plant Physiology Jan 2018Peroxisomes are small organelles that house many oxidative reactions. Peroxisome proliferation is induced under multiple stress conditions, including salt stress;...
Peroxisomes are small organelles that house many oxidative reactions. Peroxisome proliferation is induced under multiple stress conditions, including salt stress; however, factors regulating this process are not well defined. We have identified a role for Arabidopsis () MAP KINASE17 (MPK17) in affecting peroxisome division in a manner that requires the known peroxisome division factor PEROXISOME AND MITOCHONDRIAL DIVISION FACTOR1 (PMD1). MPK17 and PMD1 are involved in peroxisome proliferation in response to NaCl stress. Additionally, we found that PMD1 is an actin-binding protein and that a functioning actin cytoskeleton is required for NaCl-induced peroxisome division. Our data suggest roles for MPK17 and PMD1 in influencing the numbers and cellular distribution of peroxisomes through the cytoskeleton-peroxisome connection. These findings expand our understanding of peroxisome division and potentially identify factors connecting the actin cytoskeleton and peroxisome proliferation.
Topics: Actins; Arabidopsis; Arabidopsis Proteins; Indoleacetic Acids; Membrane Proteins; Mitogen-Activated Protein Kinases; Models, Biological; Mutation; Peroxisomes; Phenotype; Polymerization; Protein Binding; Sodium Chloride
PubMed: 28931630
DOI: 10.1104/pp.17.01019 -
Free Radical Biology & Medicine Sep 2023Reduced (NADH) and oxidized (NAD) nicotinamide adenine dinucleotides are ubiquitous hydride-donating/accepting cofactors that are essential for cellular bioenergetics....
Reduced (NADH) and oxidized (NAD) nicotinamide adenine dinucleotides are ubiquitous hydride-donating/accepting cofactors that are essential for cellular bioenergetics. Peroxisomes are single-membrane-bounded organelles that are involved in multiple lipid metabolism pathways, including beta-oxidation of fatty acids, and which contain several NAD(H)-dependent enzymes. Although maintenance of NAD(H) homeostasis in peroxisomes is considered essential for peroxisomal beta-oxidation, little is known about the regulation thereof. To resolve this issue, we have developed methods to specifically measure intraperoxisomal NADH levels in human cells using peroxisome-targeted NADH biosensors. By targeted CRISPR-Cas9-mediated genome editing of human cells, we showed with these sensors that the NAD/NADH ratio in cytosol and peroxisomes are closely connected and that this crosstalk is mediated by intraperoxisomal lactate and malate dehydrogenases, generated via translational stop codon readthrough of the LDHB and MDH1 mRNAs. Our study provides evidence for the existence of two independent redox shuttle systems in human peroxisomes that regulate peroxisomal NAD/NADH homeostasis. This is the first study that shows a specific metabolic function of protein isoforms generated by translational stop codon readthrough in humans.
Topics: Humans; NAD; Codon, Terminator; Peroxisomes; Protein Biosynthesis; Oxidation-Reduction; Homeostasis
PubMed: 37355054
DOI: 10.1016/j.freeradbiomed.2023.06.020 -
Biochemical Society Transactions Oct 2015Peroxisomes are arguably the most biochemically versatile of all eukaryotic organelles. Their metabolic functions vary between different organisms, between different... (Review)
Review
Peroxisomes are arguably the most biochemically versatile of all eukaryotic organelles. Their metabolic functions vary between different organisms, between different tissue types of the same organism and even between different developmental stages or in response to changed environmental conditions. New functions for peroxisomes are still being discovered and their importance is underscored by the severe phenotypes that can arise as a result of peroxisome dysfunction. The β-oxidation pathway is central to peroxisomal metabolism, but the substrates processed are very diverse, reflecting the diversity of peroxisomes across species. Substrates for β-oxidation enter peroxisomes via ATP-binding cassette (ABC) transporters of subfamily D; (ABCD) and are activated by specific acyl CoA synthetases for further metabolism. Humans have three peroxisomal ABCD family members, which are half transporters that homodimerize and have distinct but partially overlapping substrate specificity; Saccharomyces cerevisiae has two half transporters that heterodimerize and plants have a single peroxisomal ABC transporter that is a fused heterodimer and which appears to be the single entry point into peroxisomes for a very wide variety of β-oxidation substrates. Our studies suggest that the Arabidopsis peroxisomal ABC transporter AtABCD1 accepts acyl CoA substrates, cleaves them before or during transport followed by reactivation by peroxisomal synthetases. We propose that this is a general mechanism to provide specificity to this class of transporters and by which amphipathic compounds are moved across peroxisome membranes.
Topics: ATP-Binding Cassette Transporters; Arabidopsis Proteins; Coenzyme A Ligases; Fatty Acids; Humans; Models, Molecular; Oxidation-Reduction; Peroxisomes; Protein Conformation; Saccharomyces cerevisiae Proteins
PubMed: 26517910
DOI: 10.1042/BST20150127 -
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 -
Journal of Cell Science Jul 2022Peroxisome membrane dynamics and division are essential to adapt the peroxisomal compartment to cellular needs. The peroxisomal membrane protein PEX11β (also known as...
Peroxisome membrane dynamics and division are essential to adapt the peroxisomal compartment to cellular needs. The peroxisomal membrane protein PEX11β (also known as PEX11B) and the tail-anchored adaptor proteins FIS1 (mitochondrial fission protein 1) and MFF (mitochondrial fission factor), which recruit the fission GTPase DRP1 (dynamin-related protein 1, also known as DNML1) to both peroxisomes and mitochondria, are key factors of peroxisomal division. The current model suggests that MFF is essential for peroxisome division, whereas the role of FIS1 is unclear. Here, we reveal that PEX11β can promote peroxisome division in the absence of MFF in a DRP1- and FIS1-dependent manner. We also demonstrate that MFF permits peroxisome division independently of PEX11β and restores peroxisome morphology in PEX11β-deficient patient cells. Moreover, targeting of PEX11β to mitochondria induces mitochondrial division, indicating the potential for PEX11β to modulate mitochondrial dynamics. Our findings suggest the existence of an alternative, MFF-independent pathway in peroxisome division and report a function for FIS1 in the division of peroxisomes. This article has an associated First Person interview with the first authors of the paper.
Topics: Dynamins; GTP Phosphohydrolases; Humans; Membrane Proteins; Mitochondria; Mitochondrial Dynamics; Mitochondrial Proteins; Peroxisomes
PubMed: 35678336
DOI: 10.1242/jcs.259924 -
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 -
Biological Chemistry Feb 2023Peroxisomal integrity and function are highly dependent on its membrane and soluble (matrix) components. Matrix enzymes are imported post-translationally in a folded or... (Review)
Review
Peroxisomal integrity and function are highly dependent on its membrane and soluble (matrix) components. Matrix enzymes are imported post-translationally in a folded or even oligomeric state, via a still mysterious protein translocation mechanism. They are guided to peroxisomes via the Peroxisomal Targeting Signal (PTS) sequences which are recognized by specific cytosolic receptors, Pex5, Pex7 and Pex9. Subsequently, cargo-loaded receptors bind to the docking complex in an initial step, followed by channel formation, cargo-release, receptor-recycling and -quality control. The docking complexes of different species share Pex14 as their core component but differ in composition and oligomeric state of Pex14. Here we review and highlight the latest insights on the structure and function of the peroxisomal docking complex. We summarize differences between yeast and mammals and then we integrate this knowledge into our current understanding of the import machinery.
Topics: Animals; Membrane Proteins; Peroxisomes; Protein Transport; Carrier Proteins; Saccharomyces cerevisiae; Mammals
PubMed: 36117327
DOI: 10.1515/hsz-2022-0161 -
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