Peroxisomes are organelles enclosed by a single membrane and are present in various species.The abruption of peroxisomes is correlated with peroxisome biogenesis disorders and single peroxisomal enzyme deficiencies th...Peroxisomes are organelles enclosed by a single membrane and are present in various species.The abruption of peroxisomes is correlated with peroxisome biogenesis disorders and single peroxisomal enzyme deficiencies that induce diverse diseases in different organs.However,little is known about the protein compositions and corresponding roles of heterogeneous peroxisomes in various organs.Through transcriptomic and proteomic analyses,we observed heterogenous peroxisomal components among different organs,as well as between testicular somatic cells and different developmental stages of germ cells.As Pex3 is expressed in both germ cells and Sertoli cells,we generated Pex3 germ cell-and Sertoli cell-specific knockout mice.While Pex3 deletion in Sertoli cells did not affect spermatogenesis,the deletion in germ cells resulted in male sterility,manifested as the destruction of intercellular bridges between spermatids and the formation of multinucleated giant cells.Proteomic analysis of the Pex3-deleted spermatids revealed defective expressions of peroxisomal proteins and spermiogenesis-related proteins.These findings provide new insights that PEX3-dependent peroxisomes are essential for germ cells undergoing spermiogenesis,but not for Sertoli cells.展开更多
Peroxisomes are intracellular organelles mediating a wide variety of biosynthetic and biodegradative reactions.Included among these are the metabolism of hydrogen peroxide and other reactive species,molecules whose le...Peroxisomes are intracellular organelles mediating a wide variety of biosynthetic and biodegradative reactions.Included among these are the metabolism of hydrogen peroxide and other reactive species,molecules whose levels help define the oxidative state of cells.Loss of oxidative equilibrium in cells of tissues and organs potentiates inflammatory responses which can ultimately trigger human disease.The goal of this article is to review evidence for connections between peroxisome function,oxidative stress,and inflammation in the context of human health and degenerative disease.Dysregulated points in this nexus are identified and potential remedial approaches are presented.展开更多
Mitochondria and peroxisomes are small ubiquitous organelles. They both play major roles in cell metabolism,especially in terms of fatty acid metabolism,reactive oxygen species(ROS) production,and ROS scavenging,and i...Mitochondria and peroxisomes are small ubiquitous organelles. They both play major roles in cell metabolism,especially in terms of fatty acid metabolism,reactive oxygen species(ROS) production,and ROS scavenging,and it is now clear that they metabolically interact with each other. These two organelles share some properties,such as great plasticity and high potency to adapt their form and number according to cell requirements. Their functions are connected,and any alteration in the function of mitochondria may induce changes inperoxisomal physiology. The objective of this paper was to highlight the interconnection and the crosstalk existing between mitochondria and peroxisomes. Special emphasis was placed on the best known connections between these organelles:origin,structure,and metabolic interconnections.展开更多
Peroxisomes and mitochondria are ubiquitously found organelles. They both are dynamic structures able to divide, to fuse and to undergo autophagic processes. Their activities are dependent on proteins that are, for mo...Peroxisomes and mitochondria are ubiquitously found organelles. They both are dynamic structures able to divide, to fuse and to undergo autophagic processes. Their activities are dependent on proteins that are, for most (mitochondria) or all (peroxisome) of them, synthesized in the cytosol from the nuclear genome. Nevertheless, the membrane structures and the DNA content differ between these two organelles. Mitochondria possess a small circular genome while peroxisomes don’t. The control of their dynamic is dependent on specific factors even if some of those are able to affect both. These two organelles are metabolically connected: they are both involved in lipid metabolism. They are both able to beta oxidize fatty acids and are implicated in ROS production. However, their precise function in these metabolic pathways and their physiological functions are different. While mitochondrial metabolism is closely related to energy production, peroxisome does not seem to be associated with energy production but with the production of bioactive molecules and in detoxification processes.展开更多
Pseudo-neonatal adrenoleukodystrophy (P-NALD) is a neurodegenerative disorder caused by acyl-CoA oxidase 1 (ACOX1) deficiency with subsequent impairment of peroxisomal fatty acid β-oxidation, accumulation of very lon...Pseudo-neonatal adrenoleukodystrophy (P-NALD) is a neurodegenerative disorder caused by acyl-CoA oxidase 1 (ACOX1) deficiency with subsequent impairment of peroxisomal fatty acid β-oxidation, accumulation of very long chain fatty acids (VLCFAs) and strong reduction in peroxisome abundance. Increase in peroxisome number has been previously suggested to improve peroxisomal disorders, and in this perspective, the present work was aimed at exploring whether modulation of peroxisomes abundance could be achieved in P-NALD fibroblasts. Here we showed that treatment with the natural Argan oil induced peroxisome proliferation in P-NALD fibroblasts. This induction was independent on activations of both nuclear receptor PPARα and its coactivator PGC-1α. Lipopolysaccharides (LPS) treatment, which caused inflammation, induced also a peroxisome proliferation that, in contrast, was dependent on activations of PPARα and PGC-1α. By its ability to induce peroxisome proliferation, Argan oil is suggested to be of potential therapeutic use in patients with P-NALD.展开更多
Protein ubiquitination regulates diverse cellular processes in eukaryotic organisms,from growth and development to stress response.Proteins subjected to ubiquitination can be found in virtually all subcellular locatio...Protein ubiquitination regulates diverse cellular processes in eukaryotic organisms,from growth and development to stress response.Proteins subjected to ubiquitination can be found in virtually all subcellular locations and organelles,including peroxisomes,singlemembrane and highly dynamic organelles ubiquitous in eukaryotes.Peroxisomes contain metabolic functions essential to plants and animals such as lipid catabolism,detoxification of reactive oxygen species(ROS),biosynthesis of vital hormones and cofactors,and photorespiration.Plant peroxisomes possess a complex proteome with functions varying among different tissue types and developmental stages,and during plant response to distinct environmental cues.However,how these diverse functions are regulated at the post-translational level is poorly understood,especially in plants.In this review,we summarized current knowledge of the involvement of protein ubiquitination in peroxisome protein import,remodeling,pexophagy,and metabolism,focusing on plants,and referencing discoveries from other eukaryotic systems when relevant.Based on previous ubiquitinomics studies,we compiled a list of 56 ubiquitinated Arabidopsis peroxisomal proteins whose functions are associated with all the major plant peroxisomal metabolic pathways.This discovery suggests a broad impact of protein ubiquitination on plant peroxisome functions,therefore substantiating the need to investigate this significant regulatory mechanism in peroxisomes at more depths.展开更多
Peroxisomes are small,highly dynamic,and multifunctional organelles in eukaryotes.Essential to plant survival,peroxisomes house various crucial metabolic activities,such as degradation of hydrogen peroxide(H2O2),lipid...Peroxisomes are small,highly dynamic,and multifunctional organelles in eukaryotes.Essential to plant survival,peroxisomes house various crucial metabolic activities,such as degradation of hydrogen peroxide(H2O2),lipid metabolism,photorespiration,and hormone biosynthesis and catabolism,and remodel their proteome in response to developmental and environmental changes(Hu et al.2012;Pan and Hu 2018).The four reviews and three research articles in this special issue on plant peroxisomes provide new insights into the diverse roles and dynamics of these structurally simple but functionally complicated organelles,raising exciting new questions for future investigations.展开更多
Plant peroxisomes are subcellular compartments involved in many biochemical pathways during the life cycle of a plant but also in the mechanism of response against adverse environmental conditions.These organelles hav...Plant peroxisomes are subcellular compartments involved in many biochemical pathways during the life cycle of a plant but also in the mechanism of response against adverse environmental conditions.These organelles have an active nitro-oxidative metabolism under physiological conditions but this could be exacerbated under stress situations.Furthermore,peroxisomes have the capacity to proliferateand also undergo biochemical adaptations depending on the surrounding cellular status.An important characteristic of peroxisomes is that they have a dynamic metabolism of reactive nitrogen and oxygen species(RNS and ROS)which generates two key molecules,nitric oxide(NO)and hydrogen peroxide(H2O2).These molecules can exert signaling functions by means of post-translational modifications that affect the functionality of target molecules like proteins,peptides or fatty acids.This review provides an overview of the endogenous metabolism of ROS and RNS in peroxisomes with special emphasis on polyamine and uric acid metabolism as well as the possibility that these organelles could be a source of signal molecules involved in the functional interconnection with other subcellular compartments.展开更多
The dynamic behavior of organelles is essential for plant survival under various environmental conditions. Plant organelles, with various functions,migrate along actin filaments and contact other types of organelles, ...The dynamic behavior of organelles is essential for plant survival under various environmental conditions. Plant organelles, with various functions,migrate along actin filaments and contact other types of organelles, leading to physical interactions at a specific site called the membrane contact site. Recent studies have revealed the importance of physical interactions in maintaining efficient metabolite flow between organelles.In this review, we first summarize peroxisome function under different environmental conditions and growth stages to understand organelle interactions. We then discuss current knowledge regarding the interactions between peroxisome and other organelles, i.e., the oil bodies, chloroplast, and mitochondria from the perspective of metabolic and physiological regulation, with reference to various organelle interactions and techniques for estimating organelle interactions occurring in plant cells.展开更多
Peroxisomes are small multi-functional organelles essential for plant development and growth.Plant peroxisomes play various physiological roles,including phytohormone biosynthesis,lipid catabolism,reactive oxygen spec...Peroxisomes are small multi-functional organelles essential for plant development and growth.Plant peroxisomes play various physiological roles,including phytohormone biosynthesis,lipid catabolism,reactive oxygen species metabolism and many others.Mutant an alysis dem on strated key roles for peroxisomes in plant reproduction,seed development and germination and post-germinative seedling establishment;however,the underlying mechanisms remain to be fully elucidated.This review summarizes fin dings that reveal the importance and complexity of the role of peroxisomes in the pertinent processes.Theβ-oxidation pathway plays a central role,whereas other peroxisomal pathways are also involved.Understanding the biochemical and molecular mechanisms of these peroxisomal functions will be instrumental to the improvement of crop plants.展开更多
Peanut allergy is majorly related to severe food induced allergic reactions.Several food including cow's milk,hen's eggs,soy,wheat,peanuts,tree nuts(walnuts,hazelnuts,almonds,cashews,pecans and pistachios),fis...Peanut allergy is majorly related to severe food induced allergic reactions.Several food including cow's milk,hen's eggs,soy,wheat,peanuts,tree nuts(walnuts,hazelnuts,almonds,cashews,pecans and pistachios),fish and shellfish are responsible for more than 90%of food allergies.Here,we provide promising insights using a large-scale data-driven analysis,comparing the mechanistic feature and biological relevance of different ingredients presents in peanuts,tree nuts(walnuts,almonds,cashews,pecans and pistachios)and soybean.Additionally,we have analysed the chemical compositions of peanuts in different processed form raw,boiled and dry-roasted.Using the data-driven approach we are able to generate new hypotheses to explain why nuclear receptors like the peroxisome proliferator-activated receptors(PPARs)and its isoform and their interaction with dietary lipids may have significant effect on allergic response.The results obtained from this study will direct future experimeantal and clinical studies to understand the role of dietary lipids and PPARisoforms to exert pro-inflammatory or anti-inflammatory functions on cells of the innate immunity and influence antigen presentation to the cells of the adaptive immunity.展开更多
In mammals,the timing of physiological,biochemical and behavioral processes over a 24-h period is controlled by circadian rhythms.To entrain the master clock located in the suprachiasmatic nucleus of the hypothalamus ...In mammals,the timing of physiological,biochemical and behavioral processes over a 24-h period is controlled by circadian rhythms.To entrain the master clock located in the suprachiasmatic nucleus of the hypothalamus to a precise 24-h rhythm,environmental zeitgebers are used by the circadian system.This is done primarily by signals from the retina via the retinohypothalamic tract,but other cues like exercise,feeding,temperature,anxiety,and social events have also been shown to act as non-photic zeitgebers.The recently identified myokine irisin is proposed to serve as an entraining non-photic signal of exercise.Irisin is a product of cleavage and modification from its precursor membrane fibronectin typeⅢdomain-containing protein 5(FNDC5)in response to exercise.Apart from well-known peripheral effects,such as inducing the"browning"of white adipocytes,irisin can penetrate the blood-brain barrier and display the effects on the brain.Experimental data suggest that FNDC5/irisin mediates the positive effects of physical activity on brain functions.In several brain areas,irisin induces the production of brain-derived neurotrophic factor(BDNF).In the master clock,a significant role in gating photic stimuli in the retinohypothalamic synapse for BDNF is suggested.However,the brain receptor for irisin remains unknown.In the current review,the interactions of physical activity and the irisin/BDNF axis with the circadian system are reconceptualized.展开更多
Activated G-protein-coupled receptor 39(GPR39)has been shown to attenuate inflammation by interacting with sirtuin 1(SIRT1)and peroxisome proliferator-activated receptor-γcoactivator 1α(PGC-1α).However,whether GPR3...Activated G-protein-coupled receptor 39(GPR39)has been shown to attenuate inflammation by interacting with sirtuin 1(SIRT1)and peroxisome proliferator-activated receptor-γcoactivator 1α(PGC-1α).However,whether GPR39 attenuates neuropathic pain remains unclear.In this study,we established a Sprague-Dawley rat model of spared nerve injury-induced neuropathic pain and found that GPR39 expression was significantly decreased in neurons and microglia in the spinal dorsal horn compared with sham-operated rats.Intrathecal injection of TC-G 1008,a specific agonist of GPR39,significantly alleviated mechanical allodynia in the rats with spared nerve injury,improved spinal cord mitochondrial biogenesis,and alleviated neuroinflammation.These changes were abolished by GPR39 small interfering RNA(siRNA),Ex-527(SIRT1 inhibitor),and PGC-1αsiRNA.Taken together,these findings show that GPR39 activation ameliorates mechanical allodynia by activating the SIRT1/PGC-1αpathway in rats with spared nerve injury.展开更多
Chiglitazar sodium is a new peroxisome proliferator-activated receptor(PPAR)pan-agonist with independent intellectual property rights in China.It can treat type 2 diabetes mellitus and regulate metabolism by modestly ...Chiglitazar sodium is a new peroxisome proliferator-activated receptor(PPAR)pan-agonist with independent intellectual property rights in China.It can treat type 2 diabetes mellitus and regulate metabolism by modestly activating PPARα,PPARγ,and PPARδto improve insulin sensitivity,regulate blood glucose,and promote fatty acid oxidation and utilization.Chiglitazar sodium has a significant insulin-sensitizing effect and is advantageous in reducing fasting and postprandial blood glucose levels,particularly at the 48 mg dose in patients with concomitant high triglycerides in terms of blood glucose and triglyceride level control.展开更多
The world is experiencing reflections of the intersection of two pandemics:Obesity and coronavirus disease 2019.The prevalence of obesity has tripled since 1975 worldwide,representing substantial public health costs d...The world is experiencing reflections of the intersection of two pandemics:Obesity and coronavirus disease 2019.The prevalence of obesity has tripled since 1975 worldwide,representing substantial public health costs due to its comorbidities.The adipose tissue is the initial site of obesity impairments.During excessive energy intake,it undergoes hyperplasia and hypertrophy until overt inflammation and insulin resistance turn adipocytes into dysfunctional cells that send lipotoxic signals to other organs.The pancreas is one of the organs most affected by obesity.Once lipotoxicity becomes chronic,there is an increase in insulin secretion by pancreatic beta cells,a surrogate for type 2 diabetes mellitus(T2DM).These alterations threaten the survival of the pancreatic islets,which tend to become dysfunctional,reaching exhaustion in the long term.As for the liver,lipotoxicity favors lipogenesis and impairs beta-oxidation,resulting in hepatic steatosis.This silent disease affects around 30%of the worldwide population and can evolve into end-stage liver disease.Although therapy for hepatic steatosis remains to be defined,peroxisome proliferator-activated receptors(PPARs)activation copes with T2DM management.Peroxisome PPARs are transcription factors found at the intersection of several metabolic pathways,leading to insulin resistance relief,improved thermogenesis,and expressive hepatic steatosis mitigation by increasing mitochondrial beta-oxidation.This review aimed to update the potential of PPAR agonists as targets to treat metabolic diseases,focusing on adipose tissue plasticity and hepatic and pancreatic remodeling.展开更多
Objective This study aimed to investigate the effects of the peroxisome proliferator-activated receptorδ(PPARδ)agonist GW501516 on the proliferation of pulmonary artery smooth muscle cells(PASMCs)induced by hypoxia,...Objective This study aimed to investigate the effects of the peroxisome proliferator-activated receptorδ(PPARδ)agonist GW501516 on the proliferation of pulmonary artery smooth muscle cells(PASMCs)induced by hypoxia,in order to search for new drugs for the treatment and prevention of pulmonary vascular remodeling.Methods PASMCs were incubated with different concentrations of GW501516(10,30,100 nmol/L)under the hypoxic condition.The proliferation was determined by a CCK-8 assay.The cell cycle progression was analyzed by flow cytometry.The expression of PPARδ,S phase kinase-associated protein 2(Skp2),and cell cycle-dependent kinase inhibitor p27 was detected by Western blotting.Then PASMCs were treated with 100 nmol/L GW501516,100 nmol/L mammalian target of rapamycin(mTOR)inhibitor rapamycin and/or 2µmol/L mTOR activator MHY1485 to explore the molecular mechanisms by which GW501516 reduces the proliferation of PASMCs.Results The presented data demonstrated that hypoxia reduced the expression of PPARδin an oxygen concentration-and time-dependent manner,and GW501516 decreased the proliferation of PASMCs induced by hypoxia by blocking the progression through the G0/G1 to S phase of the cell cycle.In accordance with these findings,GW501516 downregulated Skp2 and upregulated p27 in hypoxia-exposed PASMCs.Further experiments showed that rapamycin had similar effects as GW501516 in inhibiting cell proliferation,arresting the cell cycle,regulating the expression of Skp2 and p27,and inactivating mTOR in hypoxia-exposed PASMCs.Moreover,MHY1485 reversed all the beneficial effects of GW501516 on hypoxia-stimulated PASMCs.Conclusion GW501516 inhibited the proliferation of PASMCs induced by hypoxia through blocking the mTOR/Skp2/p27 signaling pathway.展开更多
BACKGROUND Non-alcoholic fatty liver disease(NAFLD)has become a prevalent cause of chronic liver disease and ranks third among the causes of transplantation.In the United States alone,annual medical costs are approxim...BACKGROUND Non-alcoholic fatty liver disease(NAFLD)has become a prevalent cause of chronic liver disease and ranks third among the causes of transplantation.In the United States alone,annual medical costs are approximately 100 billion dollars.Unfortunately,there is no Federal Drug Administration(FDA)-approved medication for its treatment.However,various clinical trials are investigating several therapeutic classes that could potentially treat NAFLD.It is valuable to have a compilation of the data available on their efficacy.AIM To assess the efficacy of cyclophilin inhibitors,fibroblast growth factor 21 analogs(FGF21),and dual and pan peroxisome proliferator-activated receptor(PPAR)agonists for treating NAFLD.METHODS A comprehensive literature search using keywords including cyclophilin inhibitor,FGF agonist,pan-PPAR agonists,dual-PPAR agonist,NAFLD,nonalcoholic steatohepatitis,and fatty liver was conducted on October 29,2022,in PubMed,EMBASE,Cochrane Library,Scopus and Web of Science.Animal and human research,case reports,and published articles in English from all countries with patients aged 18 and above were included.Only articles with a National Institutes of Health(NIH)Quality Assessment score of five or higher out of eight points were included.Articles that were narrative or systematic reviews,abstracts,not in English,focused on patients under 18 years old,did not measure outcomes of interest,were inaccessible,or had a low NIH Quality Assessment score were excluded.Each article was screened by two independent researchers evaluating relevance and quality.Resources were scored based on the NIH Quality Assessment Score;then,pertinent data was extracted in a spreadsheet and descriptively analyzed.RESULTS Of the 681 records screened,29 met the necessary criteria and were included in this review.These records included 12 human studies and 17 animal studies.Specifically,there were four studies on cyclophilin inhibitors,four on FGF agonists/analogs,eleven on pan-PPAR agonists,and ten on dual-PPAR agonists.Different investigational products were assessed:The most common cyclophilin inhibitor was NV556;FGF agonists and analogs was Efruxifermin;pan-PPAR agonists was Lanifibranor;and dual-PPAR agonists was Saroglitazar.All classes were found to be statistically efficacious for the treatment of NAFLD,with animal studies demonstrating improvement in steatosis and/or fibrosis on biopsy and human studies evidencing improvement in different metabolic parameters and/or steatosis and fibrosis on FibroScan(P<0.05).CONCLUSION The data analyzed in this review showed clinically significant improvement in individual histological features of NAFLD in both animal and human trials for all four classes,as well as good safety profiles(P<0.05).We believe this compilation of information will have positive clinical implications in obtaining an FDA-approved therapy for NAFLD.展开更多
Endometrial carcinoma(EMC)is associated with obesity;however,the underlying mechanisms have not yet been elucidated.Peroxisome proliferator-activated receptor alpha(PPARα)is a nuclear receptor that is involved in lip...Endometrial carcinoma(EMC)is associated with obesity;however,the underlying mechanisms have not yet been elucidated.Peroxisome proliferator-activated receptor alpha(PPARα)is a nuclear receptor that is involved in lipid,glucose,and energy metabolism.PPARαreportedly functions as a tumor suppressor through its effects on lipid metabolism;however,the involvement of PPARαin the development of EMC remains unclear.The present study demonstrated that the immunohistochemical expression of nuclear PPARαwas lower in EMC than in normal endometrial tissues,suggesting the tumor suppressive nature of PPARα.A treatment with the PPARαactivator,irbesartan,inhibited the EMC cell lines,Ishikawa and HEC1A,by down-regulating sterol regulatory element-binding protein 1(SREBP1)and fatty acid synthase(FAS)and up-regulating the tumor suppressor genes p21 and p27,antioxidant enzymes,and AT-rich interaction domain 1A(ARID1A).These results indicate the potential of the activation of PPARαas a novel therapeutic approach against EMC.展开更多
基金supported by grants from the National Natural Science Foundation of China(Grant No.31890784 to J.S.)National Key R&D Program(Grant No.2021YFC2700200 to X.G.)+2 种基金National Natural Science Foundation of China(Grant Nos.92068109 and 82122025 to Yan Yuan)Natural Science Foundation of the Jiangsu Higher Education Institutions of China(Grant No.21KJA310007 to Yan Yuan)Science Foundation of Gusu School(Grant No.GSKY20220101 to J.S.).
文摘Peroxisomes are organelles enclosed by a single membrane and are present in various species.The abruption of peroxisomes is correlated with peroxisome biogenesis disorders and single peroxisomal enzyme deficiencies that induce diverse diseases in different organs.However,little is known about the protein compositions and corresponding roles of heterogeneous peroxisomes in various organs.Through transcriptomic and proteomic analyses,we observed heterogenous peroxisomal components among different organs,as well as between testicular somatic cells and different developmental stages of germ cells.As Pex3 is expressed in both germ cells and Sertoli cells,we generated Pex3 germ cell-and Sertoli cell-specific knockout mice.While Pex3 deletion in Sertoli cells did not affect spermatogenesis,the deletion in germ cells resulted in male sterility,manifested as the destruction of intercellular bridges between spermatids and the formation of multinucleated giant cells.Proteomic analysis of the Pex3-deleted spermatids revealed defective expressions of peroxisomal proteins and spermiogenesis-related proteins.These findings provide new insights that PEX3-dependent peroxisomes are essential for germ cells undergoing spermiogenesis,but not for Sertoli cells.
文摘Peroxisomes are intracellular organelles mediating a wide variety of biosynthetic and biodegradative reactions.Included among these are the metabolism of hydrogen peroxide and other reactive species,molecules whose levels help define the oxidative state of cells.Loss of oxidative equilibrium in cells of tissues and organs potentiates inflammatory responses which can ultimately trigger human disease.The goal of this article is to review evidence for connections between peroxisome function,oxidative stress,and inflammation in the context of human health and degenerative disease.Dysregulated points in this nexus are identified and potential remedial approaches are presented.
文摘Mitochondria and peroxisomes are small ubiquitous organelles. They both play major roles in cell metabolism,especially in terms of fatty acid metabolism,reactive oxygen species(ROS) production,and ROS scavenging,and it is now clear that they metabolically interact with each other. These two organelles share some properties,such as great plasticity and high potency to adapt their form and number according to cell requirements. Their functions are connected,and any alteration in the function of mitochondria may induce changes inperoxisomal physiology. The objective of this paper was to highlight the interconnection and the crosstalk existing between mitochondria and peroxisomes. Special emphasis was placed on the best known connections between these organelles:origin,structure,and metabolic interconnections.
文摘Peroxisomes and mitochondria are ubiquitously found organelles. They both are dynamic structures able to divide, to fuse and to undergo autophagic processes. Their activities are dependent on proteins that are, for most (mitochondria) or all (peroxisome) of them, synthesized in the cytosol from the nuclear genome. Nevertheless, the membrane structures and the DNA content differ between these two organelles. Mitochondria possess a small circular genome while peroxisomes don’t. The control of their dynamic is dependent on specific factors even if some of those are able to affect both. These two organelles are metabolically connected: they are both involved in lipid metabolism. They are both able to beta oxidize fatty acids and are implicated in ROS production. However, their precise function in these metabolic pathways and their physiological functions are different. While mitochondrial metabolism is closely related to energy production, peroxisome does not seem to be associated with energy production but with the production of bioactive molecules and in detoxification processes.
基金Integree of the Comite Mixte Inter-universitaire Franco-Maro- cain (CMIFM, AIMA/10/238, EGIDE)
文摘Pseudo-neonatal adrenoleukodystrophy (P-NALD) is a neurodegenerative disorder caused by acyl-CoA oxidase 1 (ACOX1) deficiency with subsequent impairment of peroxisomal fatty acid β-oxidation, accumulation of very long chain fatty acids (VLCFAs) and strong reduction in peroxisome abundance. Increase in peroxisome number has been previously suggested to improve peroxisomal disorders, and in this perspective, the present work was aimed at exploring whether modulation of peroxisomes abundance could be achieved in P-NALD fibroblasts. Here we showed that treatment with the natural Argan oil induced peroxisome proliferation in P-NALD fibroblasts. This induction was independent on activations of both nuclear receptor PPARα and its coactivator PGC-1α. Lipopolysaccharides (LPS) treatment, which caused inflammation, induced also a peroxisome proliferation that, in contrast, was dependent on activations of PPARα and PGC-1α. By its ability to induce peroxisome proliferation, Argan oil is suggested to be of potential therapeutic use in patients with P-NALD.
基金supported by the Leading Innovative and Entrepreneur Team Introduction Program of Zhejiang(No.2019R01002)Key Research Project of Zhejiang Laboratory(No.2021PE0AC04)+3 种基金Scientific Research Fund of Zhejiang Provincial Education Department(No.Y202148338)Zhejiang University Student Research Practice Program(No.P2021041)to R.P.by the National Science Foundation(No.MCB 2148206)US Department of Energy(No.DEFG02-91ER20021)to J.H。
文摘Protein ubiquitination regulates diverse cellular processes in eukaryotic organisms,from growth and development to stress response.Proteins subjected to ubiquitination can be found in virtually all subcellular locations and organelles,including peroxisomes,singlemembrane and highly dynamic organelles ubiquitous in eukaryotes.Peroxisomes contain metabolic functions essential to plants and animals such as lipid catabolism,detoxification of reactive oxygen species(ROS),biosynthesis of vital hormones and cofactors,and photorespiration.Plant peroxisomes possess a complex proteome with functions varying among different tissue types and developmental stages,and during plant response to distinct environmental cues.However,how these diverse functions are regulated at the post-translational level is poorly understood,especially in plants.In this review,we summarized current knowledge of the involvement of protein ubiquitination in peroxisome protein import,remodeling,pexophagy,and metabolism,focusing on plants,and referencing discoveries from other eukaryotic systems when relevant.Based on previous ubiquitinomics studies,we compiled a list of 56 ubiquitinated Arabidopsis peroxisomal proteins whose functions are associated with all the major plant peroxisomal metabolic pathways.This discovery suggests a broad impact of protein ubiquitination on plant peroxisome functions,therefore substantiating the need to investigate this significant regulatory mechanism in peroxisomes at more depths.
文摘Peroxisomes are small,highly dynamic,and multifunctional organelles in eukaryotes.Essential to plant survival,peroxisomes house various crucial metabolic activities,such as degradation of hydrogen peroxide(H2O2),lipid metabolism,photorespiration,and hormone biosynthesis and catabolism,and remodel their proteome in response to developmental and environmental changes(Hu et al.2012;Pan and Hu 2018).The four reviews and three research articles in this special issue on plant peroxisomes provide new insights into the diverse roles and dynamics of these structurally simple but functionally complicated organelles,raising exciting new questions for future investigations.
基金supported by an ERDF-cofinanced grant from the Ministry of Economy and Competitiveness (AGL2015-65104-P)Junta de Andalucía (group BIO-192),Spain
文摘Plant peroxisomes are subcellular compartments involved in many biochemical pathways during the life cycle of a plant but also in the mechanism of response against adverse environmental conditions.These organelles have an active nitro-oxidative metabolism under physiological conditions but this could be exacerbated under stress situations.Furthermore,peroxisomes have the capacity to proliferateand also undergo biochemical adaptations depending on the surrounding cellular status.An important characteristic of peroxisomes is that they have a dynamic metabolism of reactive nitrogen and oxygen species(RNS and ROS)which generates two key molecules,nitric oxide(NO)and hydrogen peroxide(H2O2).These molecules can exert signaling functions by means of post-translational modifications that affect the functionality of target molecules like proteins,peptides or fatty acids.This review provides an overview of the endogenous metabolism of ROS and RNS in peroxisomes with special emphasis on polyamine and uric acid metabolism as well as the possibility that these organelles could be a source of signal molecules involved in the functional interconnection with other subcellular compartments.
基金supported by the Ministry of Education, Culture, Sports, Science and Technology (MEXT, KAKENHI Grant-in-Aid for Scientific Research on Innovative Areas to M.N.[No.22120007])a fund to M.N. from Wyeth Foundation
文摘The dynamic behavior of organelles is essential for plant survival under various environmental conditions. Plant organelles, with various functions,migrate along actin filaments and contact other types of organelles, leading to physical interactions at a specific site called the membrane contact site. Recent studies have revealed the importance of physical interactions in maintaining efficient metabolite flow between organelles.In this review, we first summarize peroxisome function under different environmental conditions and growth stages to understand organelle interactions. We then discuss current knowledge regarding the interactions between peroxisome and other organelles, i.e., the oil bodies, chloroplast, and mitochondria from the perspective of metabolic and physiological regulation, with reference to various organelle interactions and techniques for estimating organelle interactions occurring in plant cells.
基金grants from Zhejiang Provincial Natural Science Foundation of China (LQ19C130004)Zhejiang University (ZJU) 100 Talents Program+2 种基金Fundamental Research Funds for the Central Universitiesthe National Science Foundation (MCB 1330441)the Chemical Sciences, Geosciences and Biosciences Division, Office of Basic Energy Sciences, Office of Science, U.S. Department of Energy (DE-FG02-91ER20021)
文摘Peroxisomes are small multi-functional organelles essential for plant development and growth.Plant peroxisomes play various physiological roles,including phytohormone biosynthesis,lipid catabolism,reactive oxygen species metabolism and many others.Mutant an alysis dem on strated key roles for peroxisomes in plant reproduction,seed development and germination and post-germinative seedling establishment;however,the underlying mechanisms remain to be fully elucidated.This review summarizes fin dings that reveal the importance and complexity of the role of peroxisomes in the pertinent processes.Theβ-oxidation pathway plays a central role,whereas other peroxisomal pathways are also involved.Understanding the biochemical and molecular mechanisms of these peroxisomal functions will be instrumental to the improvement of crop plants.
文摘Peanut allergy is majorly related to severe food induced allergic reactions.Several food including cow's milk,hen's eggs,soy,wheat,peanuts,tree nuts(walnuts,hazelnuts,almonds,cashews,pecans and pistachios),fish and shellfish are responsible for more than 90%of food allergies.Here,we provide promising insights using a large-scale data-driven analysis,comparing the mechanistic feature and biological relevance of different ingredients presents in peanuts,tree nuts(walnuts,almonds,cashews,pecans and pistachios)and soybean.Additionally,we have analysed the chemical compositions of peanuts in different processed form raw,boiled and dry-roasted.Using the data-driven approach we are able to generate new hypotheses to explain why nuclear receptors like the peroxisome proliferator-activated receptors(PPARs)and its isoform and their interaction with dietary lipids may have significant effect on allergic response.The results obtained from this study will direct future experimeantal and clinical studies to understand the role of dietary lipids and PPARisoforms to exert pro-inflammatory or anti-inflammatory functions on cells of the innate immunity and influence antigen presentation to the cells of the adaptive immunity.
基金supported by the Russian Science Foundation(Grant No.23-25-00152).
文摘In mammals,the timing of physiological,biochemical and behavioral processes over a 24-h period is controlled by circadian rhythms.To entrain the master clock located in the suprachiasmatic nucleus of the hypothalamus to a precise 24-h rhythm,environmental zeitgebers are used by the circadian system.This is done primarily by signals from the retina via the retinohypothalamic tract,but other cues like exercise,feeding,temperature,anxiety,and social events have also been shown to act as non-photic zeitgebers.The recently identified myokine irisin is proposed to serve as an entraining non-photic signal of exercise.Irisin is a product of cleavage and modification from its precursor membrane fibronectin typeⅢdomain-containing protein 5(FNDC5)in response to exercise.Apart from well-known peripheral effects,such as inducing the"browning"of white adipocytes,irisin can penetrate the blood-brain barrier and display the effects on the brain.Experimental data suggest that FNDC5/irisin mediates the positive effects of physical activity on brain functions.In several brain areas,irisin induces the production of brain-derived neurotrophic factor(BDNF).In the master clock,a significant role in gating photic stimuli in the retinohypothalamic synapse for BDNF is suggested.However,the brain receptor for irisin remains unknown.In the current review,the interactions of physical activity and the irisin/BDNF axis with the circadian system are reconceptualized.
基金supported by the National Notural Science Foundation of China,Nos.82071556 and 82271291 (both to WM)
文摘Activated G-protein-coupled receptor 39(GPR39)has been shown to attenuate inflammation by interacting with sirtuin 1(SIRT1)and peroxisome proliferator-activated receptor-γcoactivator 1α(PGC-1α).However,whether GPR39 attenuates neuropathic pain remains unclear.In this study,we established a Sprague-Dawley rat model of spared nerve injury-induced neuropathic pain and found that GPR39 expression was significantly decreased in neurons and microglia in the spinal dorsal horn compared with sham-operated rats.Intrathecal injection of TC-G 1008,a specific agonist of GPR39,significantly alleviated mechanical allodynia in the rats with spared nerve injury,improved spinal cord mitochondrial biogenesis,and alleviated neuroinflammation.These changes were abolished by GPR39 small interfering RNA(siRNA),Ex-527(SIRT1 inhibitor),and PGC-1αsiRNA.Taken together,these findings show that GPR39 activation ameliorates mechanical allodynia by activating the SIRT1/PGC-1αpathway in rats with spared nerve injury.
文摘Chiglitazar sodium is a new peroxisome proliferator-activated receptor(PPAR)pan-agonist with independent intellectual property rights in China.It can treat type 2 diabetes mellitus and regulate metabolism by modestly activating PPARα,PPARγ,and PPARδto improve insulin sensitivity,regulate blood glucose,and promote fatty acid oxidation and utilization.Chiglitazar sodium has a significant insulin-sensitizing effect and is advantageous in reducing fasting and postprandial blood glucose levels,particularly at the 48 mg dose in patients with concomitant high triglycerides in terms of blood glucose and triglyceride level control.
基金the Conselho Nacional de Desenvolvimento Científico e Tecnológico(Brazil),No.303785/2020-9Fundação Carlos Chagas Filho de AmparoàPesquisa do Estado do Rio de Janeiro,No.E-26/200.984/2022 for V.S-M.
文摘The world is experiencing reflections of the intersection of two pandemics:Obesity and coronavirus disease 2019.The prevalence of obesity has tripled since 1975 worldwide,representing substantial public health costs due to its comorbidities.The adipose tissue is the initial site of obesity impairments.During excessive energy intake,it undergoes hyperplasia and hypertrophy until overt inflammation and insulin resistance turn adipocytes into dysfunctional cells that send lipotoxic signals to other organs.The pancreas is one of the organs most affected by obesity.Once lipotoxicity becomes chronic,there is an increase in insulin secretion by pancreatic beta cells,a surrogate for type 2 diabetes mellitus(T2DM).These alterations threaten the survival of the pancreatic islets,which tend to become dysfunctional,reaching exhaustion in the long term.As for the liver,lipotoxicity favors lipogenesis and impairs beta-oxidation,resulting in hepatic steatosis.This silent disease affects around 30%of the worldwide population and can evolve into end-stage liver disease.Although therapy for hepatic steatosis remains to be defined,peroxisome proliferator-activated receptors(PPARs)activation copes with T2DM management.Peroxisome PPARs are transcription factors found at the intersection of several metabolic pathways,leading to insulin resistance relief,improved thermogenesis,and expressive hepatic steatosis mitigation by increasing mitochondrial beta-oxidation.This review aimed to update the potential of PPAR agonists as targets to treat metabolic diseases,focusing on adipose tissue plasticity and hepatic and pancreatic remodeling.
基金supported by the National Natural Science Foundation of Hubei Province(No.2018CFC801).
文摘Objective This study aimed to investigate the effects of the peroxisome proliferator-activated receptorδ(PPARδ)agonist GW501516 on the proliferation of pulmonary artery smooth muscle cells(PASMCs)induced by hypoxia,in order to search for new drugs for the treatment and prevention of pulmonary vascular remodeling.Methods PASMCs were incubated with different concentrations of GW501516(10,30,100 nmol/L)under the hypoxic condition.The proliferation was determined by a CCK-8 assay.The cell cycle progression was analyzed by flow cytometry.The expression of PPARδ,S phase kinase-associated protein 2(Skp2),and cell cycle-dependent kinase inhibitor p27 was detected by Western blotting.Then PASMCs were treated with 100 nmol/L GW501516,100 nmol/L mammalian target of rapamycin(mTOR)inhibitor rapamycin and/or 2µmol/L mTOR activator MHY1485 to explore the molecular mechanisms by which GW501516 reduces the proliferation of PASMCs.Results The presented data demonstrated that hypoxia reduced the expression of PPARδin an oxygen concentration-and time-dependent manner,and GW501516 decreased the proliferation of PASMCs induced by hypoxia by blocking the progression through the G0/G1 to S phase of the cell cycle.In accordance with these findings,GW501516 downregulated Skp2 and upregulated p27 in hypoxia-exposed PASMCs.Further experiments showed that rapamycin had similar effects as GW501516 in inhibiting cell proliferation,arresting the cell cycle,regulating the expression of Skp2 and p27,and inactivating mTOR in hypoxia-exposed PASMCs.Moreover,MHY1485 reversed all the beneficial effects of GW501516 on hypoxia-stimulated PASMCs.Conclusion GW501516 inhibited the proliferation of PASMCs induced by hypoxia through blocking the mTOR/Skp2/p27 signaling pathway.
文摘BACKGROUND Non-alcoholic fatty liver disease(NAFLD)has become a prevalent cause of chronic liver disease and ranks third among the causes of transplantation.In the United States alone,annual medical costs are approximately 100 billion dollars.Unfortunately,there is no Federal Drug Administration(FDA)-approved medication for its treatment.However,various clinical trials are investigating several therapeutic classes that could potentially treat NAFLD.It is valuable to have a compilation of the data available on their efficacy.AIM To assess the efficacy of cyclophilin inhibitors,fibroblast growth factor 21 analogs(FGF21),and dual and pan peroxisome proliferator-activated receptor(PPAR)agonists for treating NAFLD.METHODS A comprehensive literature search using keywords including cyclophilin inhibitor,FGF agonist,pan-PPAR agonists,dual-PPAR agonist,NAFLD,nonalcoholic steatohepatitis,and fatty liver was conducted on October 29,2022,in PubMed,EMBASE,Cochrane Library,Scopus and Web of Science.Animal and human research,case reports,and published articles in English from all countries with patients aged 18 and above were included.Only articles with a National Institutes of Health(NIH)Quality Assessment score of five or higher out of eight points were included.Articles that were narrative or systematic reviews,abstracts,not in English,focused on patients under 18 years old,did not measure outcomes of interest,were inaccessible,or had a low NIH Quality Assessment score were excluded.Each article was screened by two independent researchers evaluating relevance and quality.Resources were scored based on the NIH Quality Assessment Score;then,pertinent data was extracted in a spreadsheet and descriptively analyzed.RESULTS Of the 681 records screened,29 met the necessary criteria and were included in this review.These records included 12 human studies and 17 animal studies.Specifically,there were four studies on cyclophilin inhibitors,four on FGF agonists/analogs,eleven on pan-PPAR agonists,and ten on dual-PPAR agonists.Different investigational products were assessed:The most common cyclophilin inhibitor was NV556;FGF agonists and analogs was Efruxifermin;pan-PPAR agonists was Lanifibranor;and dual-PPAR agonists was Saroglitazar.All classes were found to be statistically efficacious for the treatment of NAFLD,with animal studies demonstrating improvement in steatosis and/or fibrosis on biopsy and human studies evidencing improvement in different metabolic parameters and/or steatosis and fibrosis on FibroScan(P<0.05).CONCLUSION The data analyzed in this review showed clinically significant improvement in individual histological features of NAFLD in both animal and human trials for all four classes,as well as good safety profiles(P<0.05).We believe this compilation of information will have positive clinical implications in obtaining an FDA-approved therapy for NAFLD.
基金supported by JSPS KAKENHI Grant Number 18K09285.
文摘Endometrial carcinoma(EMC)is associated with obesity;however,the underlying mechanisms have not yet been elucidated.Peroxisome proliferator-activated receptor alpha(PPARα)is a nuclear receptor that is involved in lipid,glucose,and energy metabolism.PPARαreportedly functions as a tumor suppressor through its effects on lipid metabolism;however,the involvement of PPARαin the development of EMC remains unclear.The present study demonstrated that the immunohistochemical expression of nuclear PPARαwas lower in EMC than in normal endometrial tissues,suggesting the tumor suppressive nature of PPARα.A treatment with the PPARαactivator,irbesartan,inhibited the EMC cell lines,Ishikawa and HEC1A,by down-regulating sterol regulatory element-binding protein 1(SREBP1)and fatty acid synthase(FAS)and up-regulating the tumor suppressor genes p21 and p27,antioxidant enzymes,and AT-rich interaction domain 1A(ARID1A).These results indicate the potential of the activation of PPARαas a novel therapeutic approach against EMC.
