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Cell Biochemistry and Biophysics 2000Peroxisomes in liver parenchymal cells proliferate in response to structurally diverse nonmutagenic compounds designated as peroxisome proliferators (PP). Sustained... (Review)
Review
Peroxisomes in liver parenchymal cells proliferate in response to structurally diverse nonmutagenic compounds designated as peroxisome proliferators (PP). Sustained induction of peroxisome proliferation and peroxisomal fatty acid beta-oxidation system in rats and mice leads to the development of liver tumors. Two mechanistic issues are important for consideration: elucidation of the upstream events responsible for the tissue and species specific induction of the characteristic pleiotropic responses by PPs; and delineation of the downstream events associated with peroxisome proliferation, and their role in the development of liver tumors in species that are sensitive to the induction of peroxisome proliferation. The induction of peroxisome proliferation is mediated by PP-activated receptor alpha (PPAR alpha), a member of a group of transcription factors that regulate the expression of genes associated with lipid metabolism and adipocyte differentiation. Three isotypes of this family of nuclear receptors, namely PPAR alpha, PPAR gamma, and PPAR delta (also called beta), have been identified as products of separate genes. Although PPAR alpha is responsible for the PP-induced pleiotropic responses, PPAR gamma seems to be involved in adipogenesis and differentiation, but the events associated with PPAR gamma do not directly involve peroxisomes and peroxisome proliferation. PPARs heterodimerize with 9-cis retinoic acid receptor (RXR), and bind to PP response element(s) (PPREs) on the target gene promoter to initiate inducible transcriptional activity. Tissue and species responses to PPs depend on pharmacokinetics, relative abundance of PPAR isotypes, nature of PPRE in the upstream regions of target genes, the extent of competition or cross-talk among nuclear transcription factors for PPAR heterodimerization partner retinoid X receptor and the modulating role of coactivators and corepressors on ligand-dependent transcription of PPARs. Using PPAR as bait in the yeast two-hybrid system, the authors recently cloned mouse steroid receptor coactivator-1 (SRC-1) and PPAR-binding protein (PBP), and identified them as PPAR coactivators. Both SRC-1 and PBP contain LXXLL signature motifs, considered necessary and sufficient for the binding of coactivators to nuclear receptors. A multifaceted approach, which includes the identification of additional coactivators that may be responsible for cell specific transcriptional activation of PPAR-mediated target genes, and generation of genetically modified animals (transgenic and gene disrupted), will be necessary to gain more insight into the upstream and downstream targets responsible for the induction of early and delayed PP-induced pleiotropic responses. In this context, it is important to note that mice deficient in fatty acyl-CoA oxidase, the first and rate-limiting enzyme of the peroxisomal beta-oxidation system, revealed that this enzyme is indispensable for the physiological regulation of PPAR alpha, and the absence of this enzyme leads to sustained transcriptional activation of genes regulated by this receptor.
Topics: Animals; Gene Expression Regulation; Humans; Liver; Peroxisomes; Receptors, Cytoplasmic and Nuclear; Signal Transduction; Transcription Factors
PubMed: 11330046
DOI: 10.1385/cbb:32:1-3:187 -
The Journal of Cell Biology Apr 2011The biogenesis of peroxisomal matrix and membrane proteins is substantially different from the biogenesis of proteins of other subcellular compartments, such as... (Review)
Review
The biogenesis of peroxisomal matrix and membrane proteins is substantially different from the biogenesis of proteins of other subcellular compartments, such as mitochondria and chloroplasts, that are of endosymbiotic origin. Proteins are targeted to the peroxisome matrix through interactions between specific targeting sequences and receptor proteins, followed by protein translocation across the peroxisomal membrane. Recent advances have shed light on the nature of the peroxisomal translocon in matrix protein import and the molecular mechanisms of receptor recycling. Furthermore, the endoplasmic reticulum has been shown to play an important role in peroxisomal membrane protein biogenesis. Defining the molecular events in peroxisome assembly may enhance our understanding of the etiology of human peroxisome biogenesis disorders.
Topics: Animals; Endoplasmic Reticulum; Humans; Membrane Proteins; Peroxisomes
PubMed: 21464226
DOI: 10.1083/jcb.201010022 -
Trends in Cell Biology Sep 2004Many organisms stringently regulate the number, volume and enzymatic content of peroxisomes (and other organelles). Understanding this regulation requires knowledge of... (Review)
Review
Many organisms stringently regulate the number, volume and enzymatic content of peroxisomes (and other organelles). Understanding this regulation requires knowledge of how organelles are assembled and selectively destroyed in response to metabolic cues. In the past decade, considerable progress has been achieved in the elucidation of the roles of genes involved in peroxisome biogenesis, half of which are affected in human peroxisomal disorders. The recent discovery of intermediates and genes in peroxisome turnover by selective autophagy-related processes (pexophagy) opens the door to understanding peroxisome turnover and homeostasis. In this article, we summarize advances in the characterization of genes that are necessary for the transport and delivery of selective and nonselective cargoes to the lysosome or vacuole by autophagy-related processes, with emphasis on peroxisome turnover by micropexophagy.
Topics: Animals; Autophagy; Biological Transport; Fungal Proteins; Humans; Hydrolysis; Lysosomes; Microscopy, Fluorescence; Models, Biological; Peroxisomes; Pichia; Saccharomyces cerevisiae; Signal Transduction; Vacuoles
PubMed: 15350980
DOI: 10.1016/j.tcb.2004.07.014 -
Annual Review of Microbiology 2012Peroxisomes are core eukaryotic organelles that generally function in lipid metabolism and detoxification of reactive oxygen species, but they are increasingly... (Review)
Review
Peroxisomes are core eukaryotic organelles that generally function in lipid metabolism and detoxification of reactive oxygen species, but they are increasingly associated with taxa-specific metabolic, cellular, and developmental functions. Here, we present a brief overview of peroxisome assembly, followed by a discussion of their functional diversification. Matrix protein import occurs through a remarkable translocon that can accommodate folded and even oligomeric proteins. Metabolically specialized peroxisomes include glycosomes of trypanosomes, which have come to compartmentalize most of the glycolytic pathway and play a role in developmental signal transduction. The differentiation of physically distinct subcompartments also contributes to peroxisome diversification; in the clade of filamentous ascomycetes, dense-core Woronin bodies bud from peroxisomes to gate cell-to-cell channels. Here, the import of oligomeric cargo is central to the mechanism of subcompartment specification. In general, the acquisition of a tripeptide peroxisome targeting signal by nonperoxisomal proteins appears to be a recurrent step in the evolution of peroxisome diversity.
Topics: Eukaryota; Metabolic Networks and Pathways; Peroxisomes; Signal Transduction
PubMed: 22994494
DOI: 10.1146/annurev-micro-092611-150126 -
Biochemical Society Transactions Jun 2010Peroxisomes are eukaryotic organelles with crucial functions in development. Plant peroxisomes participate in various metabolic processes, some of which are co-operated... (Review)
Review
Peroxisomes are eukaryotic organelles with crucial functions in development. Plant peroxisomes participate in various metabolic processes, some of which are co-operated by peroxisomes and other organelles, such as mitochondria and chloroplasts. Defining the complete picture of how these essential organelles divide and proliferate will be instrumental in understanding how the dynamics of peroxisome abundance contribute to changes in plant physiology and development. Research in Arabidopsis thaliana has identified several evolutionarily conserved major components of the peroxisome division machinery, including five isoforms of PEROXIN11 proteins (PEX11), two dynamin-related proteins (DRP3A and DRP3B) and two FISSION1 proteins (FIS1A/BIGYIN and FIS1B). Recent studies in our laboratory have also begun to uncover plant-specific factors. DRP5B is a dual-localized protein that is involved in the division of both chloroplasts and peroxisomes, representing an invention of the plant/algal lineage in organelle division. In addition, PMD1 (peroxisomal and mitochondrial division 1) is a plant-specific protein tail anchored to the outer surface of peroxisomes and mitochondria, mediating the division and/or positioning of these organelles. Lastly, light induces peroxisome proliferation in dark-grown Arabidopsis seedlings, at least in part, through activating the PEX11b gene. The far-red light receptor phyA (phytochrome A) and the transcription factor HYH (HY5 homologue) are key components in this signalling pathway. In summary, pathways for the division and proliferation of plant peroxisomes are composed of conserved and plant-specific factors. The sharing of division proteins by peroxisomes, mitochondria and chloroplasts is also suggesting possible co-ordination in the division of these metabolically associated plant organelles.
Topics: Algal Proteins; Arabidopsis; Arabidopsis Proteins; Chloroplasts; Humans; Light; Mitochondria; Peroxisomes
PubMed: 20491669
DOI: 10.1042/BST0380817 -
Annual Review of Cell and Developmental... 2007Eukaryotic cells divide their metabolic labor between functionally distinct, membrane-enveloped organelles, each precisely tailored for a specific set of biochemical... (Review)
Review
Eukaryotic cells divide their metabolic labor between functionally distinct, membrane-enveloped organelles, each precisely tailored for a specific set of biochemical reactions. Peroxisomes are ubiquitous, endoplasmic reticulum-derived organelles that perform requisite biochemical functions intimately connected to lipid metabolism. Upon cell division, cells have to strictly control peroxisome division and inheritance to maintain an appropriate number of peroxisomes in each cell. Peroxisome division follows a specific sequence of events that include peroxisome elongation, membrane constriction, and peroxisome fission. Pex11 proteins mediate the elongation step of peroxisome division, whereas dynamin-related proteins execute the final fission. The mechanisms responsible for peroxisome membrane constriction are poorly understood. Molecular players involved in peroxisome inheritance are just beginning to be elucidated. Inp1p and Inp2p are two recently identified peroxisomal proteins that perform antagonistic functions in regulating peroxisome inheritance in budding yeast. Inp1p promotes the retention of peroxisomes in mother cells and buds by attaching peroxisomes to as-yet-unidentified cortical structures. Inp2p is implicated in the motility of peroxisomes by linking them to the Myo2p motor, which then propels their movement along actin cables. The functions of Inp1p and Inp2p are cell cycle regulated and coordinated to ensure a fair distribution of peroxisomes at cytokinesis.
Topics: Animals; Cell Division; Eukaryotic Cells; Humans; Membrane Proteins; Peroxisomes; Saccharomyces cerevisiae
PubMed: 17506702
DOI: 10.1146/annurev.cellbio.23.090506.123456 -
Annual Review of Biochemistry 2013Looks can be deceiving. Although peroxisomes appear to be simple organelles, their formation and maintenance pose unique challenges for the cell. The birth of new... (Review)
Review
Looks can be deceiving. Although peroxisomes appear to be simple organelles, their formation and maintenance pose unique challenges for the cell. The birth of new peroxisomes starts at the endoplasmic reticulum (ER), which delivers lipids and membrane proteins. To form a new peroxisomal compartment, ER-derived preperoxisomal vesicles carrying different membrane proteins fuse, allowing the assembly of the peroxisomal translocon. To complete formation, peroxisomes import their soluble proteins directly from the cytosol using the newly assembled translocon. Together with the ER-derived biogenic route, peroxisomal fission and segregation subsequently maintain the cellular peroxisome population. In this review we highlight the latest insights on the life cycle of peroxisomes and show how the new cell biology concept of peroxisome formation affects our thinking about peroxisome-related diseases and their evolutionary past. The future challenge lies in the identification of all the proteins involved in this elaborate biogenic process and the dissection of their mechanism of action.
Topics: Animals; Endoplasmic Reticulum; Humans; Membrane Proteins; Peroxisomes; Protein Transport
PubMed: 23414306
DOI: 10.1146/annurev-biochem-081111-125123 -
Current Opinion in Cell Biology Aug 2014Significant progress has been made towards our understanding of the mechanism of peroxisome formation, in particular concerning sorting of peroxisomal membrane proteins,... (Review)
Review
Significant progress has been made towards our understanding of the mechanism of peroxisome formation, in particular concerning sorting of peroxisomal membrane proteins, matrix protein import and organelle multiplication. Here we evaluate the progress made in recent years. We focus mainly on progress made in yeasts. We indicate the gaps in our knowledge and discuss conflicting models.
Topics: Animals; Endoplasmic Reticulum; Humans; Models, Biological; Peroxisomes; Protein Biosynthesis; Protein Transport; Proteins
PubMed: 24681485
DOI: 10.1016/j.ceb.2014.02.002 -
Cell Cycle (Georgetown, Tex.) 2017Peroxisomes are essential and dynamic organelles that allow cells to rapidly adapt and cope with changing environments and/or physiological conditions by modulation of... (Review)
Review
Peroxisomes are essential and dynamic organelles that allow cells to rapidly adapt and cope with changing environments and/or physiological conditions by modulation of both peroxisome biogenesis and turnover. Peroxisome biogenesis involves the assembly of peroxisome membranes and the import of peroxisomal matrix proteins. The latter depends on the receptor, PEX5, which recognizes peroxisomal matrix proteins in the cytosol directly or indirectly, and transports them to the peroxisomal lumen. In this review, we discuss the role of PEX5 ubiquitination in both peroxisome biogenesis and turnover, specifically in PEX5 receptor recycling, stability and abundance, as well as its role in pexophagy (autophagic degradation of peroxisomes).
Topics: Animals; Autophagy; Homeostasis; Humans; Peroxisome-Targeting Signal 1 Receptor; Peroxisomes; Receptors, Cytoplasmic and Nuclear; Ubiquitination
PubMed: 28933989
DOI: 10.1080/15384101.2017.1376149 -
Sub-cellular Biochemistry 2013Ca(2+) homeostasis in peroxisomes has been an unsolved problem for many years. Recently novel probes to monitor Ca(2+) levels in the lumen of peroxisomes in living cells... (Review)
Review
Ca(2+) homeostasis in peroxisomes has been an unsolved problem for many years. Recently novel probes to monitor Ca(2+) levels in the lumen of peroxisomes in living cells of both animal and plant cells have been developed. Here we discuss the contrasting results obtained in mammalian cells with chemiluminecsent (aequorin) and fluorescent (cameleon) probes targeted to peroxisomes. We briefly discuss the different characteristics of these probes and the possible pitfalls of the two approaches. We conclude that the contrasting results obtained with the two probes may reflect a heterogeneity among peroxisomes in mammalian cells. We also discuss the results obtained in plant peroxisomes. In particular we demonstrate that Ca(2+) increases in the cytoplasm are mirrored by similar rises of Ca(2+) concentration the lumen of peroxisomes. The increases in peroxisome Ca(2+) level results in the activation of a catalase isoform, CAT3. Other functional roles of peroxisomal Ca(2+) changes in plant physiology are briefly discussed.
Topics: Animals; Biosensing Techniques; Calcium; Calcium Signaling; Homeostasis; Humans; Kinetics; Luminescent Measurements; Peroxisomes; Plants
PubMed: 23821146
DOI: 10.1007/978-94-007-6889-5_7