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Current Protein & Peptide Science 2023
Topics: Peroxisomes; Membrane Proteins; Cell Proliferation
PubMed: 36803754
DOI: 10.2174/1389203724666230220121638 -
Advances in Experimental Medicine and... 2020Peroxisome is an organelle conserved in almost all eukaryotic cells with a variety of functions in cellular metabolism, including fatty acid β-oxidation, synthesis of... (Review)
Review
Peroxisome is an organelle conserved in almost all eukaryotic cells with a variety of functions in cellular metabolism, including fatty acid β-oxidation, synthesis of ether glycerolipid plasmalogens, and redox homeostasis. Such metabolic functions and the exclusive importance of peroxisomes have been highlighted in fatal human genetic disease called peroxisomal biogenesis disorders (PBDs). Recent advances in this field have identified over 30 PEX genes encoding peroxins as essential factors for peroxisome biogenesis in various species from yeast to humans. Functional delineation of the peroxins has revealed that peroxisome biogenesis comprises the processes, involving peroxisomal membrane assembly, matrix protein import, division, and proliferation. Catalase, the most abundant peroxisomal enzyme, catalyzes decomposition of hydrogen peroxide. Peroxisome plays pivotal roles in the cellular redox homeostasis and the response to oxidative stresses, depending on intracellular localization of catalase.
Topics: Humans; Intracellular Membranes; Metabolic Networks and Pathways; Oxidation-Reduction; Oxidative Stress; Peroxisomal Disorders; Peroxisomes; Protein Transport
PubMed: 33417203
DOI: 10.1007/978-3-030-60204-8_1 -
Microscopy Research and Technique Jun 2003Peroxisome proliferators comprise a heterogeneous group of compounds known for their ability to cause massive proliferation of peroxisomes and liver carcinogenesis in... (Review)
Review
Peroxisome proliferators comprise a heterogeneous group of compounds known for their ability to cause massive proliferation of peroxisomes and liver carcinogenesis in rodents. In recent years it has become evident that other animals may be threatened by peroxisome proliferators, in particular aquatic organisms living in coastal and estuarine areas. These animals are exposed to a variety of pollutants of industrial, agricultural and urban origin which are potential peroxisome proliferators. Both laboratory and field studies have shown that phthalate ester plasticizers, PAHs and oil derivatives, PCBs, certain pesticides, bleached kraft pulp and paper mill effluents, alkylphenols and estrogens provoke peroxisome proliferation in different fish or bivalve mollusc species. The response appears to be mediated by peroxisome-proliferator activated receptors, members of the nuclear receptor family, recently cloned in fish. Based on these results it is proposed that peroxisome proliferation could be used as a biomarker of exposure to a variety of pollutants in environmental pollution assessment. This is illustrated by a case study in which mussels, used worldwide as sentinels of environmental pollution, were transplanted from reference to contaminated areas and vice versa. In mussels native to an area polluted with PAHs and PCBs, peroxisomal acyl-CoA oxidase (AOX) activity and peroxisomal volume density were 2-3 fold and 5-fold higher, respectively, compared to the reference site. When animals were transplanted to the polluted station, with increased concentration of organic xenobiotics, a concomitant significant increase of AOX was recorded. Conversely, in animals transplanted to the cleaner station, AOX activity and peroxisomal volume density decreased significantly. These results indicate that peroxisome proliferation is a rapid (i.e., two days) and reversible response to pollution in mussels. Before peroxisome proliferation can be implemented as a biomarker in biomonitoring programs, a well-defined protocol should be established and validated in intercalibration and quality assurance programmes. Furthermore, the influence of biotic and abiotic factors, some of which are known to affect peroxisome proliferation (season, tide level, interpopulation and interindividual variability), should be taken into consideration. The possible hepatocarcinogenic effects as well as the potential adverse effects on reproduction, development, and growth of peroxisome proliferators are unknown in aquatic organisms, thus providing a challenge for future investigations.
Topics: Acyl-CoA Oxidase; Animals; Biomarkers; Bivalvia; Environmental Monitoring; Fishes; Oxidoreductases; Peroxisome Proliferators; Peroxisomes; Receptors, Cytoplasmic and Nuclear; Transcription Factors; Water Pollutants, Chemical
PubMed: 12740826
DOI: 10.1002/jemt.10329 -
Current Genetics Apr 2022Peroxisomes are single membrane-bound organelles ubiquitously present in several cell types and are associated with cell and tissue-specific functions. Their role in...
Peroxisomes are single membrane-bound organelles ubiquitously present in several cell types and are associated with cell and tissue-specific functions. Their role in cellular ageing is under investigation in various model systems. Metabolism of cellular reactive oxygen species is a universal function performed by these organelles. In this study, we investigated alterations in peroxisome number upon early replicative ageing of yeast cells. Increase in the number of peroxisomes in replicatively aged mother cells of wild-type yeast was observed when cultured in both peroxisome-inducing and non-inducing medium. Further, we investigated if this increase in peroxisome number in replicatively aged cells is due to enhanced peroxisome proliferation. For this, the number of peroxisomes in replicatively aged mother cells of pex11, pex25 and pex11pex25 was analysed. Increased percentage of aged cells was observed in pex25 and pex11pex25 cells cultured in peroxisome-inducing oleic acid medium. Interestingly, when cultured in oleic acid, young mother cells devoid of Pex11 showed reduced peroxisome proliferation compared to old mother cells. Induced activity of the antioxidant enzyme catalase and reduced accumulation of reactive oxygen species were reported in all studied strains when cultured in oleic acid medium. Further, our data also suggest that replicatively aged cells with increased peroxisome number also display mitochondrial dysfunction and fragmentation in all the strains studied. In conclusion, our data suggests a correlation between increase in peroxisome number and replicative age of yeast cells and interestingly this increase seems to be partly dependent on the fission proteins.
Topics: Cell Proliferation; Membrane Proteins; Peroxins; Peroxisomes; Saccharomyces cerevisiae; Saccharomyces cerevisiae Proteins
PubMed: 35220444
DOI: 10.1007/s00294-022-01233-3 -
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 -
Free Radical Biology & Medicine Nov 2023In peroxisomes, acyl-CoA oxidase (ACOX) oxidizes fatty acids and produces HO, and the latter is decomposed by catalase. If ethanol is present, ethanol will be oxidized...
In peroxisomes, acyl-CoA oxidase (ACOX) oxidizes fatty acids and produces HO, and the latter is decomposed by catalase. If ethanol is present, ethanol will be oxidized by catalase coupling with decomposition of HO. Peroxisome proliferator-activated receptor α (PPARα) agonist WY-14,643 escalated ethanol clearance, which was not observed in catalase knockout (Cat) mice or partially blocked by an ACOX1 inhibitor. WY-14,643 induced peroxisome proliferation via peroxin 16 (PEX16). PEX16 liver-specific knockout (Pex16) mice lack intact peroxisomes in liver, but catalase and ACOX1 were upregulated. Due to lacking intact peroxisomes, the upregulated catalase and ACOX1 in the Pex16 mice were mislocated in cytosol and microsomes, and the escalated ethanol clearance was not observed in the Pex16 mice, implicating that the intact functional peroxisomes are essential for ACOX1/catalase to metabolize ethanol. Alcohol-associated liver disease (ALD) is a spectrum of liver disorders ranging from alcoholic steatosis to steatohepatitis. WY-14,643 ameliorated alcoholic steatosis but tended to enhance alcoholic steatohepatitis. In mice lacking nuclear factor erythroid 2-related factor 2 (Nrf2), WY-14,643 still induced PEX16, ACOX1 and catalase to escalate ethanol clearance and blunt alcoholic steatosis, which was not observed in the PPARα-absent Nrf2 mice (Pparα/Nrf2) mice, suggesting that WY-14,643 escalates ethanol clearance through PPARα but not through Nrf2.
Topics: Animals; Mice; Acyl-CoA Oxidase; Catalase; Cell Proliferation; Ethanol; Fatty Liver; Hydrogen Peroxide; Liver; Mice, Knockout; NF-E2-Related Factor 2; Peroxisomes; PPAR alpha
PubMed: 37567517
DOI: 10.1016/j.freeradbiomed.2023.08.016 -
Food and Chemical Toxicology : An... Nov 1993Peroxisomes are subcellular organelles found in all eukaryotic cells. In the liver they are usually round and measure about 0.5-1.0 microns; in rodents they contain a... (Review)
Review
Peroxisomes are subcellular organelles found in all eukaryotic cells. In the liver they are usually round and measure about 0.5-1.0 microns; in rodents they contain a prominent crystalloid core, but this may be absent in newly formed rodent peroxisomes as well as in human peroxisomes. A major role of the peroxisomes is the breakdown of long-chain fatty acids, thereby complementing mitochondrial fatty-acid metabolism. Many chemicals are known to increase the number of peroxisomes in rat and mouse hepatocytes. This peroxisome proliferation is accompanied by replicative DNA synthesis and liver growth. No clear structure-activity relationships are apparent. Many of these peroxisome proliferators contain acid functions that can modulate fatty acid metabolism. Two mechanisms have been proposed for the induction of peroxisome proliferation. One is based on the existence of one or several specific cytosolic receptors that bind the peroxisome proliferator, facilitating its translocation to the cell nucleus and the activation of the expression of specific genes. The second, perhaps more general, hypothesis involves chemically mediated perturbation of lipid metabolism. These two hypotheses are not mutually exclusive. Many peroxisome proliferators have been shown to induce hepatocellular tumours, despite being uniformly non-genotoxic, when administered at high dose levels to rats and mice for long periods. Three mechanisms have been proposed to explain the induction of tumours. One is based on increased production of active oxygen species due to imbalanced production of peroxisomal enzymes; it has been proposed that these reactive oxygen species cause indirect DNA damage with subsequent tumour formation. In rodents, an alternative mechanism is the promotion of endogenous lesions by sustained DNA synthesis and hyperplasia. Thirdly, it is conceivable that sustained growth stimulation may be sufficient for tumour formation. Marked species differences are apparent in response to peroxisome proliferations. Rats and mice are extremely sensitive, and hamsters show an intermediate response while guinea pigs, monkeys and humans appear to be relatively insensitive or non-responsive at dose levels that produce a marked response in rodents. These species differences may be reproduced in vitro using primary culture hepatocytes isolated from a variety of species including humans. The available experimental evidence suggests a strong association and a probable casual link between peroxisome-proliferator-elicited liver growth and the subsequent development of liver tumours in rats and mice. Since humans are insensitive or unresponsive, at therapeutic dose levels, to peroxisome-proliferator-induced hepatic effects, it is reasonable to conclude that the encountered levels of exposure to these non-genotoxic agents do not present a hepatocarcinogenic hazard to humans.(ABSTRACT TRUNCATED AT 400 WORDS)
Topics: Animals; Carcinogens; Cell Division; Female; Humans; Hyperplasia; Hypertrophy; Lipid Metabolism; Liver; Liver Neoplasms; Male; Microbodies; Rodentia; Species Specificity; Structure-Activity Relationship
PubMed: 8258416
DOI: 10.1016/0278-6915(93)90225-n -
Current Opinion in Plant Biology Dec 2009Peroxisomes are highly dynamic subcellular organelles that undergo proliferation in response to a variety of environmental stimuli. The past few years have witnessed the... (Review)
Review
Peroxisomes are highly dynamic subcellular organelles that undergo proliferation in response to a variety of environmental stimuli. The past few years have witnessed the identification and characterization of several key classes of proteins required for peroxisome division and proliferation in Arabidopsis. These include the PEROXIN11 (PEX11) family, the dynamin-related proteins (DRPs), and the FISSION1 (FIS1) proteins, some of which are shared by the division machineries of peroxisomes and other organelles. Recent studies have also uncovered a role for the photoreceptor phyA and the bZIP transcription factor HY5 homolog (HYH) in regulating light-induced peroxisome proliferation in Arabidopsis. In this review we attempt to summarize the current state of our knowledge of peroxisome division/proliferation and their regulation in plants.
Topics: Arabidopsis; Arabidopsis Proteins; Carrier Proteins; Cell Cycle; DNA-Binding Proteins; Dynamins; Gene Expression Regulation, Plant; Light; Membrane Proteins; Peroxins; Peroxisomes; Phytochrome A; Protein Processing, Post-Translational
PubMed: 19734083
DOI: 10.1016/j.pbi.2009.08.001 -
Environmental Health Perspectives May 2001Di(2-ethylhexyl)phthalate (DEHP), a peroxisome proliferator, has been listed by the International Agency for Research on Cancer (IARC) and by the National Toxicology... (Review)
Review
Di(2-ethylhexyl)phthalate (DEHP), a peroxisome proliferator, has been listed by the International Agency for Research on Cancer (IARC) and by the National Toxicology Program as a possible or reasonably anticipated human carcinogen because it induces dose-related increases in liver tumors in both sexes of rats and mice. Recently, the suggestion has been advanced that DEHP should be considered unlikely to be a human carcinogen because it is claimed that the carcinogenic effects of this agent in rodents are due to peroxisome proliferation and that humans are nonresponsive to this process. An IARC working group recently downgraded DEHP to "not classifiable as to its carcinogenicity to humans" because they concluded that DEHP produces liver tumors in rats and mice by a mechanism involving peroxisome proliferation, which they considered to be not relevant to humans. The literature review presented in this commentary reveals that, although our knowledge of the mechanism of peroxisome proliferation has advanced greatly over the past 10 years, our understanding of the mechanism(s) of carcinogenicty of peroxisome proliferators remains incomplete. Most important is that published studies have not established peroxisome proliferation per se as an obligatory pathway in the carcinogenicity of DEHP. No epidemiologic studies have been reported on the potential carcinogenicity of DEHP, and cancer epidemiologic studies of hypolipidemic fibrate drugs (peroxisome proliferators) are inconclusive. Most of the pleiotropic effects of peroxisome proliferators are mediated by the peroxisome proliferator activated receptor (PPAR), a ligand-activated transcription factor that is expressed at lower levels in humans than in rats and mice. In spite of this species difference in PPAR expression, hypolipidemic fibrates have been shown to induce hypolipidemia in humans and to modulate gene expression (e.g., genes regulating lipid homeostasis) in human hepatocytes by PPAR activation. Thus, humans are responsive to agents that induce peroxisome proliferation in rats and mice. Because peroxisome proliferators can affect multiple signaling pathways by transcriptional activation of PPAR-regulated genes, it is likely that alterations in specific regulated pathways (e.g., suppression of apoptosis, protooncogene expression) are involved in tumor induction by peroxisome proliferators. In addition, because DEHP also induces biological effects that occur independently of peroxisome proliferation (e.g., morphologic cell transformation and decreased levels of gap junction intercellular communication), it is possible that some of these responses also contribute to the carcinogenicity of this chemical. Last, species differences in tissue expression of PPARs indicate that it may not be appropriate to expect exact site correspondence for potential PPAR-mediated effects induced by peroxisome proliferators in animals and humans. Because peroxisome proliferation has not been established as an obligatory step in the carcinogenicity of DEHP, the contention that DEHP poses no carcinogenic risk to humans because of species differences in peroxisome proliferation should be viewed as an unvalidated hypothesis.
Topics: Animals; Apoptosis; Carcinogenicity Tests; Carcinogens; Cell Division; Diethylhexyl Phthalate; Humans; Liver Neoplasms; Mice; Peroxisome Proliferators; Peroxisomes; Rats; Receptors, Cytoplasmic and Nuclear; Risk Assessment; Signal Transduction; Species Specificity; Transcription Factors
PubMed: 11401753
DOI: 10.1289/ehp.01109437 -
ELife Apr 2022How environmental cues influence peroxisome proliferation, particularly through organelles, remains largely unknown. Yeast peroxisomes metabolize fatty acids (FA), and...
How environmental cues influence peroxisome proliferation, particularly through organelles, remains largely unknown. Yeast peroxisomes metabolize fatty acids (FA), and methylotrophic yeasts also metabolize methanol. NADH and acetyl-CoA, produced by these pathways enter mitochondria for ATP production and for anabolic reactions. During the metabolism of FA and/or methanol, the mitochondrial oxidative phosphorylation (OXPHOS) pathway accepts NADH for ATP production and maintains cellular redox balance. Remarkably, peroxisome proliferation in Pichia pastoris was abolished in NADH-shuttling- and OXPHOS mutants affecting complex I or III, or by the mitochondrial uncoupler, 2,4-dinitrophenol (DNP), indicating ATP depletion causes the phenotype. We show that mitochondrial OXPHOS deficiency inhibits expression of several peroxisomal proteins implicated in FA and methanol metabolism, as well as in peroxisome division and proliferation. These genes are regulated by the Snf1 complex (SNF1), a pathway generally activated by a high AMP/ATP ratio. In OXPHOS mutants, Snf1 is activated by phosphorylation, but Gal83, its interacting subunit, fails to translocate to the nucleus. Phenotypic defects in peroxisome proliferation observed in the OXPHOS mutants, and phenocopied by the Δgal83 mutant, were rescued by deletion of three transcriptional repressor genes (MIG1, MIG2, and NRG1) controlled by SNF1 signaling. Our results are interpreted in terms of a mechanism by which peroxisomal and mitochondrial proteins and/or metabolites influence redox and energy metabolism, while also influencing peroxisome biogenesis and proliferation, thereby exemplifying interorganellar communication and interplay involving peroxisomes, mitochondria, cytosol, and the nucleus. We discuss the physiological relevance of this work in the context of human OXPHOS deficiencies.
Topics: Adenosine Triphosphate; Cell Proliferation; Genes, Fungal; Humans; Methanol; Mitochondrial Diseases; NAD; Oxidative Phosphorylation; Peroxisomes; Protein Serine-Threonine Kinases; Repressor Proteins; Saccharomycetales; Signal Transduction
PubMed: 35467529
DOI: 10.7554/eLife.75143