4,325 results match your criteria Peroxisomal Disorders


ERR and dPECR Suggest a Link Between Neuroprotection and the Regulation of Ethanol Consumption Preference.

Front Psychiatry 2021 26;12:655816. Epub 2021 Apr 26.

Institute of Zoology, University of Köln, Köln, Germany.

Reconsumption of ethanol after withdrawal is a hallmark for relapse in recovering patients with alcohol use disorders. We show that the preference of to reconsume ethanol after abstinence shares mechanistic similarities to human behavior by feeding the antirelapse drug acamprosate to flies and reducing the ethanol consumption preference. The cellular stress mutant also reduced ethanol consumption preference. Read More

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Compound heterozygous p. Arg949Trp and p. Gly970Ala mutations deteriorated the function of PEX1p: A study on PEX1 in a patient with Zellweger syndrome.

J Cell Biochem 2021 May 6. Epub 2021 May 6.

Department of Cell and Molecular Biology and Microbiology, Faculty of Biological Science and Technology, University of Isfahan, Isfahan, Postal Code 81746-73441, Iran.

The peroxisome is responsible for a variety of vital pathways in primary metabolism, including the very long-chain fatty-acid oxidation and plasmalogen lipid biosynthesis. Autosomal recessive disorder of the Zellweger spectrum (ZSD) is a major subset of peroxisome biogenesis disorders (PBDs) that can be caused by mutations in any of the 14 PEX genes. Zellweger syndrome (ZS) is the foremost common and severe phenotype within the heterogeneous ZSD. Read More

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The Unity of Redox and Structural Remodeling of Brown Adipose Tissue in Hypothyroidism.

Antioxidants (Basel) 2021 Apr 12;10(4). Epub 2021 Apr 12.

Center for Electron Microscopy, Faculty of Biology, University of Belgrade, 11000 Belgrade, Serbia.

Brown adipose tissue (BAT) is important for maintaining whole-body metabolic and energy homeostasis. However, the effects of hypothyroidism, one of the most common diseases worldwide, which increases the risk of several metabolic disorders, on BAT redox and metabolic homeostasis remain mostly unknown. We aimed to investigate the dynamics of protein expression, enzyme activity, and localization of antioxidant defense (AD) enzymes in rat interscapular BAT upon induction of hypothyroidism by antithyroid drug methimazole for 7, 15, and 21 days. Read More

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Peroxisomal Disorders and Their Mouse Models Point to Essential Roles of Peroxisomes for Retinal Integrity.

Int J Mol Sci 2021 Apr 15;22(8). Epub 2021 Apr 15.

Lab of Cell Metabolism, Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, 3000 Leuven, Belgium.

Peroxisomes are multifunctional organelles, well known for their role in cellular lipid homeostasis. Their importance is highlighted by the life-threatening diseases caused by peroxisomal dysfunction. Importantly, most patients suffering from peroxisomal biogenesis disorders, even those with a milder disease course, present with a number of ocular symptoms, including retinopathy. Read More

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Mitochondrial Fission Factor Gene Mutation: A Dilemma for Prenatal Diagnosis.

Int J Appl Basic Med Res 2021 Apr-Jun;11(2):114-116. Epub 2021 Apr 8.

Departments of Obstetrics and Gynaecology, AIIMS, Jodhpur, Rajasthan, India.

Mitochondrial fission factor (MFF) gene mutations are rare mitochondrial fission disorders, resulting in autosomal recessive neurological disorders. We here report a rare case of MFF gene mutation running in a family which ultimately turned out to be a variant of unknown significance. A 29-year-old multigravida visited at 18-week gestation for prenatal genetic testing as her previous baby had cerebral palsy and global developmental delay. Read More

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Endothelial ether lipids link the vasculature to blood pressure, behavior, and neurodegeneration.

J Lipid Res 2021 Apr 21:100079. Epub 2021 Apr 21.

Division of Endocrinology, Metabolism & Lipid Research, Department of Medicine, Washington University, St. Louis, MO 63110, USA; Departments of Cell Biology & Physiology, Washington University, St. Louis, MO 63110, USA. Electronic address:

Vascular disease contributes to neurodegeneration, which is associated with decreased blood pressure in older humans. Plasmalogens, ether phospholipids produced by peroxisomes, are decreased in Alzheimer's disease, Parkinson's disease and other neurodegenerative disorders. However, the mechanistic links between ether phospholipids, blood pressure, and neurodegeneration are not fully understood. Read More

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Autophagy Inhibitors Do Not Restore Peroxisomal Functions in Cells With the Most Common Peroxisome Biogenesis Defect.

Front Cell Dev Biol 2021 1;9:661298. Epub 2021 Apr 1.

Laboratory Genetic Metabolic Diseases, Amsterdam Gastroenterology, Endocrinology and Metabolism, Amsterdam University Medical Centers - Location AMC, University of Amsterdam, Amsterdam, Netherlands.

Peroxisome biogenesis disorders within the Zellweger spectrum (PBD-ZSDs) are most frequently associated with the c.2528G>A (p.G843D) mutation in the gene (PEX1-G843D), which results in impaired import of peroxisomal matrix proteins and, consequently, defective peroxisomal functions. Read More

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Mitochondrial Fission Protein 1: Emerging Roles in Organellar Form and Function in Health and Disease.

Front Endocrinol (Lausanne) 2021 25;12:660095. Epub 2021 Mar 25.

Department of Biochemistry, Medical College of Wisconsin, Milwaukee, WI, United States.

Mitochondrial fission protein 1 (Fis1) was identified in yeast as being essential for mitochondrial division or fission and subsequently determined to mediate human mitochondrial and peroxisomal fission. Yet, its exact functions in humans, especially in regard to mitochondrial fission, remains an enigma as genetic deletion of Fis1 elongates mitochondria in some cell types, but not others. Fis1 has also been identified as an important component of apoptotic and mitophagic pathways suggesting the protein may have multiple, essential roles. Read More

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Attenuation of 7-ketocholesterol- and 7β-hydroxycholesterol-induced oxiapoptophagy by nutrients, synthetic molecules and oils: Potential for the prevention of age-related diseases.

Ageing Res Rev 2021 Mar 24;68:101324. Epub 2021 Mar 24.

Team Bio-PeroxIL 'Biochemistry of the Peroxisome, Inflammation and Lipid Metabolism' (EA 7270), University Bourgogne Franche-Comté (UBFC), Inserm, Dijon, France. Electronic address:

Age-related diseases for which there are no effective treatments include cardiovascular diseases; neurodegenerative diseases such as Alzheimer's disease; eye disorders such as cataract and age-related macular degeneration; and, more recently, Severe Acute Respiratory Syndrome (SARS-CoV-2). These diseases are associated with plasma and/or tissue increases in cholesterol derivatives mainly formed by auto-oxidation: 7-ketocholesterol, also known as 7-oxo-cholesterol, and 7β-hydroxycholesterol. The formation of these oxysterols can be considered as a consequence of mitochondrial and peroxisomal dysfunction, leading to increased in oxidative stress, which is accentuated with age. Read More

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Neurofilament light chain as a potential biomarker for monitoring neurodegeneration in X-linked adrenoleukodystrophy.

Nat Commun 2021 03 22;12(1):1816. Epub 2021 Mar 22.

Department of Pathobiology of the Nervous System, Center for Brain Research, Medical University of Vienna, Vienna, Austria.

X-linked adrenoleukodystrophy (X-ALD), the most frequent monogenetic disorder of brain white matter, is highly variable, ranging from slowly progressive adrenomyeloneuropathy (AMN) to life-threatening inflammatory brain demyelination (CALD). In this study involving 94 X-ALD patients and 55 controls, we tested whether plasma/serum neurofilament light chain protein (NfL) constitutes an early distinguishing biomarker. In AMN, we found moderately elevated NfL with increased levels reflecting higher grading of myelopathy-related disability. Read More

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mediator subunit is a key regulator of hepatic autophagy and lipid metabolism.

Autophagy 2021 Mar 18:1-19. Epub 2021 Mar 18.

Program of Cardiovascular & Metabolic Disorders, Duke-NUS Medical School Singapore, Singapore.

Hepatic macroautophagy/autophagy and fatty acid metabolism are transcriptionally regulated by nuclear receptors (NRs); however, it is not known whether their transcriptional co-activators are involved in autophagy. We thus examined MED1 (mediator complex subunit 1), a key component of the Mediator Complex that directly interacts with NRs, on these processes. We found that knockdown (KD) in cultured hepatic cells decreased autophagy and mitochondrial activity that was accompanied by decreased transcription of genes involved in these processes. Read More

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Plasmalogen-Based Liquid Crystalline Multiphase Structures Involving Docosapentaenoyl Derivatives Inspired by Biological Cubic Membranes.

Front Cell Dev Biol 2021 11;9:617984. Epub 2021 Feb 11.

Wenzhou Institute, University of Chinese Academy of Sciences, Wenzhou, China.

Structural properties of plasmenyl-glycerophospholipids (plasmalogens) have been scarcely studied for plasmalogens with long polyunsaturated fatty acid (PUFA) chains, despite of their significance for the organization and functions of the cellular membranes. Elaboration of supramolecular assemblies involving PUFA-chain plasmalogens in nanostructured mixtures with lyotropic lipids may accelerate the development of nanomedicines for certain severe pathologies (e.g. Read More

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February 2021

Twins with PEX7 related intellectual disability and cataract: Highlighting phenotypes of peroxisome biogenesis disorder 9B.

Am J Med Genet A 2021 05 14;185(5):1504-1508. Epub 2021 Feb 14.

Department of Medical Genetics, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, India.

Peroxisome biogenesis disorders (PBDs) are a group of autosomal recessive disorders caused due to impaired peroxisome assembly affecting the formation of functional peroxisomes. PBDs are caused by a mutation in PEX gene family resulting in disease manifestation with extreme variability ranging from the onset of profound neurologic symptoms in newborns to progressive degenerative disease in adults. Disease causing variations in PEX7 is known to cause severe rhizomelic chondrodysplasia punctata type 1 and PBD 9B, an allelic disorder resulting in a milder phenotype, often indistinguishable from that of classic Refsum disease. Read More

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A Novel Mutation in PEX11β Gene.

Iran J Child Neurol 2021 ;15(1):93-100

Department of pediatric endocrinology and metabolism, Mofid Children's Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

PEX11β ([OMIM] 614920) mutation causes an extremely rare subgroup of peroxisomal biogenesis disorders, with only six cases reported to date. In this article, we reported a patient with episodic migraine-like attacks, delirium, mood and behavior change, polyneuropathy, and history of congenital cataract. Whole exome sequencing showed novel c. Read More

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January 2021

Depletion of HNRNPA1 induces peroxisomal autophagy by regulating PEX1 expression.

Biochem Biophys Res Commun 2021 03 3;545:69-74. Epub 2021 Feb 3.

School of Life Sciences, BK21 FOUR KNU Creative BioResearch Group, Kyungpook National University, Daegu, 41566, South Korea. Electronic address:

Peroxisomes play an essential role in cellular homeostasis by regulating lipid metabolism and the conversion of reactive oxygen species (ROS). Several peroxisomal proteins, known as peroxins (PEXs), control peroxisome biogenesis and degradation. Various mutations in the PEX genes are genetic causes for the development of inheritable peroxisomal-biogenesis disorders, such as Zellweger syndrome. Read More

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Gene Expression Analysis of Mevalonate Kinase Deficiency Affected Children Identifies Molecular Signatures Related to Hematopoiesis.

Int J Environ Res Public Health 2021 01 28;18(3). Epub 2021 Jan 28.

Department of Medicine, Surgery and Dentistry 'Scuola Medica Salernitana', University of Salerno, Via Salvatore Allende, 84081 Baronissi (SA), Italy.

Mevalonate kinase deficiency (MKD) is a rare autoinflammatory genetic disorder characterized by recurrent fever attacks and systemic inflammation with potentially severe complications. Although it is recognized that the lack of protein prenylation consequent to mevalonate pathway blockade drives IL1β hypersecretion, and hence autoinflammation, MKD pathogenesis and the molecular mechanisms underlaying most of its clinical manifestations are still largely unknown. In this study, we performed a comprehensive bioinformatic analysis of a microarray dataset of MKD patients, using gene ontology and Ingenuity Pathway Analysis (IPA) tools, in order to identify the most significant differentially expressed genes and infer their predicted relationships into biological processes, pathways, and networks. Read More

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January 2021

Eyes See what the Mind Knows: Clues to Pattern Recognition in Single Enzyme Deficiency-Related Peroxisomal Disorders.

Mol Syndromol 2020 Dec 30;11(5-6):309-314. Epub 2020 Sep 30.

Institute of Medical Genetics and Genomics, Sir Ganga Ram Hospital, New Delhi, India.

Peroxisomal disorders are a heterogeneous group of inborn errors of metabolism that result in impaired function of the peroxisome. Within this, single enzyme deficiencies are known to cause a constellation of symptoms not very different from the peroxisome biogenesis defects. Thus, there is a need to identify features that differentiate the two. Read More

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December 2020

[A pedigree of X-linked adrenoleukodystrophy with hypocorticism].

Zhonghua Nei Ke Za Zhi 2021 Feb;60(2):152-155

Department of Endocrinology, Peking University International Hospital, Beijing 102200, China.

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February 2021

Anti-oxidant MitoQ rescue of AWB chemosensory neuron impairment in a model of X-linked Adrenoleukodystrophy.

MicroPubl Biol 2021 Jan 14;2021. Epub 2021 Jan 14.

Faculty of Medicine, University of Vic-Central University of Catalonia (UVic-UCC), 08500 Vic, Spain.

X-linked Adrenoleukodystrophy (X-ALD) is a neurometabolic disorder caused by a defective peroxisomal ABCD1 transporter of very long-chain fatty acids (VLCFAs). We have characterized a nematode model of X-ALD with loss of the gene, the worm orthologue of . These mutants recapitulated the key hallmarks of X-ALD and importantly mitochondria targeted antioxidant MitoQ prevented axonal degeneration and locomotor disability. Read More

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January 2021

The Drosophila melanogaster as Genetic Model System to Dissect the Mechanisms of Disease that Lead to Neurodegeneration in Adrenoleukodystrophy.

Adv Exp Med Biol 2020 ;1299:145-159

Department of Microbiology and Immunology, Dalhousie University, Halifax, Canada.

Drosophila melanogaster is the most successful genetic model organism to study different human disease with a recent increased popularity to study neurological disorders. Drosophila melanogaster has a complex yet well-defined brain with defined anatomical regions with specific functions. The neuronal network in the adult brain has a structural organization highly similar to human neurons, but in a brain that is much more amenable for complex analyses. Read More

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February 2021

A Mouse Model System to Study Peroxisomal Roles in Neurodegeneration of Peroxisome Biogenesis Disorders.

Adv Exp Med Biol 2020 ;1299:119-143

Institute of Rheological Functions of Food, Fukuoka, Japan.

Fourteen PEX genes are currently identified as genes responsible for peroxisome biogenesis disorders (PBDs). Patients with PBDs manifest as neurodegenerative symptoms such as neuronal migration defect and malformation of the cerebellum. To address molecular mechanisms underlying the pathogenesis of PBDs, mouse models for the PBDs have been generated by targeted disruption of Pex genes. Read More

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February 2021

Heimler Syndrome.

Adv Exp Med Biol 2020 ;1299:81-87

Reference Center for Rare Diseases "Genetic deafness", Filière Santé Maladies rares SENSGENE, European Reference Network ERN CRANIO, Federation of Genetic, Necker-Enfants Malades Hospital, Paris, France.

Heimler syndrome is a rare syndrome associating sensorineural hearing loss with retinal dystrophy and amelogenesis imperfecta due to PEX1 or PEX6 biallelic pathogenic variations. This syndrome is one of the less severe forms of peroxisome biogenesis disorders. In this chapter, we will review clinical, biological, and genetic knowledges about the Heimler syndrome. Read More

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February 2021

Zellweger Syndrome Disorders: From Severe Neonatal Disease to Atypical Adult Presentation.

Authors:
David Cheillan

Adv Exp Med Biol 2020 ;1299:71-80

Inserm U1060 - CarMeN Laboratory, Lyon University, Pierre-Bénite, France.

Zellweger syndrome disorders (ZSD) is the principal group of peroxisomal disorders characterized by a defect of peroxisome biogenesis due to mutations in one of the 13 PEX genes. The clinical spectrum is very large with a continuum from antenatal forms to adult presentation. Whereas biochemical profile in body fluids is classically used for their diagnosis, the revolution of high-throughput sequencing has extended the knowledge about these disorders. Read More

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February 2021

Fatty Acid Oxidation in Peroxisomes: Enzymology, Metabolic Crosstalk with Other Organelles and Peroxisomal Disorders.

Adv Exp Med Biol 2020 ;1299:55-70

Departments of Clinical Chemistry and Pediatrics, Amsterdam Gastroenterology Endocrinology Metabolism, Laboratory Genetic Metabolic Diseases and Emma Children's hospital, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.

Peroxisomes play a central role in metabolism as exemplified by the fact that many genetic disorders in humans have been identified through the years in which there is an impairment in one or more of these peroxisomal functions, in most cases associated with severe clinical signs and symptoms. One of the key functions of peroxisomes is the β-oxidation of fatty acids which differs from the oxidation of fatty acids in mitochondria in many respects which includes the different substrate specificities of the two organelles. Whereas mitochondria are the main site of oxidation of medium-and long-chain fatty acids, peroxisomes catalyse the β-oxidation of a distinct set of fatty acids, including very-long-chain fatty acids, pristanic acid and the bile acid intermediates di- and trihydroxycholestanoic acid. Read More

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February 2021

Peroxisome Biogenesis Disorders.

Adv Exp Med Biol 2020 ;1299:45-54

Institute of Rheological Functions of Food, Fukuoka, Japan.

Peroxisomes are presented in all eukaryotic cells and play essential roles in many of lipid metabolic pathways, including β-oxidation of fatty acids and synthesis of ether-linked glycerophospholipids, such as plasmalogens. Impaired peroxisome biogenesis, including defects of membrane assembly, import of peroxisomal matrix proteins, and division of peroxisome, causes peroxisome biogenesis disorders (PBDs). Fourteen complementation groups of PBDs are found, and their complementing genes termed PEXs are isolated. Read More

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February 2021

7-Ketocholesterol- and 7β-Hydroxycholesterol-Induced Peroxisomal Disorders in Glial, Microglial and Neuronal Cells: Potential Role in Neurodegeneration : 7-ketocholesterol and 7β-hydroxycholesterol-Induced Peroxisomal Disorders and Neurodegeneration.

Adv Exp Med Biol 2020 ;1299:31-41

Team 'Biochemistry of the Peroxisome, Inflammation and Lipid Metabolism' EA 7270/University of Bourgogne Franche-Comté/Inserm, Dijon, France.

Peroxisomopathies are qualitative or quantitative deficiencies in peroxisomes which lead to increases in the level of very-long-chain fatty acids (VLCFA) and can be associated with more or less pronounced dysfunction of central nervous system cells: glial and microglial cells. Currently, in frequent neurodegenerative diseases, Alzheimer's disease (AD) and multiple sclerosis (MS), peroxisomal dysfunction is also suspected due to an increase in VLCFA, which can be associated with a decrease of plasmalogens, in these patients. Moreover, in patients suffering from peroxisomopathies, such as X-linked adrenoleukodystrophy (X-ALD), AD, or MS, the increase in oxidative stress observed leads to the formation of cytotoxic oxysterols: 7-ketocholesterol (7KC) and 7β-hydroxycholesterol (7β-OHC). Read More

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February 2021

Peroxisomal Dysfunction and Oxidative Stress in Neurodegenerative Disease: A Bidirectional Crosstalk.

Adv Exp Med Biol 2020 ;1299:19-30

Department of Cellular and Molecular Medicine, Laboratory of Lipid Biochemistry and Protein Interactions, KU Leuven, Leuven, Belgium.

Peroxisomes are multifunctional organelles best known for their role in cellular lipid and hydrogen peroxide metabolism. In this chapter, we review and discuss the diverse functions of this organelle in brain physiology and neurodegeneration, with a particular focus on oxidative stress. We first briefly summarize what is known about the various nexuses among peroxisomes, the central nervous system, oxidative stress, and neurodegenerative disease. Read More

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February 2021

Peroxisome: Metabolic Functions and Biogenesis.

Adv Exp Med Biol 2020 ;1299:3-17

Institute of Rheological Functions of Food, Fukuoka, Japan.

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. Read More

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February 2021

Expanded Carrier Screening and the Complexity of Implementation.

Obstet Gynecol 2021 02;137(2):345-350

Department of Obstetrics, Gynecology, and Reproductive Sciences, University of California, San Francisco, San Francisco, California.

Advances in genetic technology have allowed for the development of multiplex panels that can test for hundreds of genetic disorders at the same time; these large panels are referred to as expanded carrier screening. This process can screen couples for far more conditions than the gene-by-gene approach used with traditional carrier screening; however, although expanded carrier screening has been promoted as an efficient means of detecting many more disorders, the complexities of genetic sequencing raise substantial challenges and concerns. In our practice, we have seen a number of complex cases in which only attention to detail on the part of thorough genetic counselors allowed identification of misclassified variants that could have resulted in significant patient harm. Read More

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February 2021

Peroxisomes of the Brain: Distribution, Functions, and Associated Diseases.

Neurotox Res 2021 Jun 5;39(3):986-1006. Epub 2021 Jan 5.

Organelle Biology and Cellular Ageing Lab, Department of Biosciences and Bioengineering, Indian Institute of Technology Guwahati, Guwahati, 781039, Assam, India.

Peroxisomes are versatile cell organelles that exhibit a repertoire of organism and cell-type dependent functions. The presence of oxidases and antioxidant enzymes is a characteristic feature of these organelles. The role of peroxisomes in various cell types in human health and disease is under investigation. Read More

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