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Biochimica Et Biophysica Acta May 2016The peroxisomal compartment in hepatocytes hosts several essential metabolic conversions. These are defective in peroxisomal disorders that are either caused by failure... (Review)
Review
The peroxisomal compartment in hepatocytes hosts several essential metabolic conversions. These are defective in peroxisomal disorders that are either caused by failure to import the enzymes in the organelle or by mutations in the enzymes or in transporters needed to transfer the substrates across the peroxisomal membrane. Hepatic pathology is one of the cardinal features in disorders of peroxisome biogenesis and peroxisomal β-oxidation although it only rarely determines the clinical fate. In mouse models of these diseases liver pathologies also occur, although these are not always concordant with the human phenotype which might be due to differences in diet, expression of enzymes and backup mechanisms. Besides the morphological changes, we overview the impact of peroxisome malfunction on other cellular compartments including mitochondria and the ER. We further focus on the metabolic pathways that are affected such as bile acid formation, and dicarboxylic acid and branched chain fatty acid degradation. It appears that the association between deregulated metabolites and pathological events remains unclear.
Topics: Animals; Disease Models, Animal; Endoplasmic Reticulum; Gene Expression Regulation; Humans; Liver; Membrane Proteins; Metabolic Networks and Pathways; Mice; Mitochondria, Liver; Mutation; Peroxisomal Disorders; Peroxisomes; Protein Isoforms; Protein Transport; Signal Transduction
PubMed: 26453805
DOI: 10.1016/j.bbamcr.2015.09.035 -
Biochimica Et Biophysica Acta May 2016Peroxisomes are highly dynamic organelles that can rapidly change in size, abundance, and protein content in response to alterations in nutritional and other... (Review)
Review
Peroxisomes are highly dynamic organelles that can rapidly change in size, abundance, and protein content in response to alterations in nutritional and other environmental conditions. These dynamic changes in peroxisome features, referred to as peroxisome dynamics, rely on the coordinated action of several processes of peroxisome biogenesis. Revealing the regulatory mechanisms of peroxisome dynamics is an emerging theme in cell biology. These mechanisms are inevitably linked to and synchronized with the biogenesis and degradation of peroxisomes. To date, the key players and basic principles of virtually all steps in the peroxisomal life cycle are known, but regulatory mechanisms remained largely elusive. A number of recent studies put the spotlight on reversible protein phosphorylation for the control of peroxisome dynamics and highlighted peroxisomes as hubs for cellular signal integration and regulation. Here, we will present and discuss the results of several studies performed using yeast and mammalian cells that convey a sense of the impact protein phosphorylation may have on the modulation of peroxisome dynamics by regulating peroxisomal matrix and membrane protein import, proliferation, inheritance, and degradation. We further put forward the idea to make use of current data on phosphorylation sites of peroxisomal and peroxisome-associated proteins reported in advanced large-scale phosphoproteomic studies.
Topics: Animals; Autophagy; Gene Expression Regulation; Glycerol-3-Phosphate Dehydrogenase (NAD+); Humans; Membrane Proteins; Membrane Transport Proteins; Mice; Organelle Biogenesis; Peroxisomal Targeting Signal 2 Receptor; Peroxisome-Targeting Signal 1 Receptor; Peroxisomes; Phosphorylation; Protein Isoforms; Protein Transport; Receptors, Cytoplasmic and Nuclear; Saccharomyces cerevisiae; Saccharomyces cerevisiae Proteins; Signal Transduction
PubMed: 26775584
DOI: 10.1016/j.bbamcr.2015.12.022 -
Cell Reports Oct 2023The enhanced response of glucagon and its Drosophila homolog, adipokinetic hormone (Akh), leads to high-caloric-diet-induced hyperglycemia across species. While previous...
The enhanced response of glucagon and its Drosophila homolog, adipokinetic hormone (Akh), leads to high-caloric-diet-induced hyperglycemia across species. While previous studies have characterized regulatory components transducing linear Akh signaling promoting carbohydrate production, the spatial elucidation of Akh action at the organelle level still remains largely unclear. In this study, we find that Akh phosphorylates extracellular signal-regulated kinase (ERK) and translocates it to peroxisome via calcium/calmodulin-dependent protein kinase II (CaMKII) cascade to increase carbohydrate production in the fat body, leading to hyperglycemia. The mechanisms include that ERK mediates fat body peroxisomal conversion of amino acids into carbohydrates for gluconeogenesis in response to Akh. Importantly, Akh receptor (AkhR) or ERK deficiency, importin-associated ERK retention from peroxisome, or peroxisome inactivation in the fat body sufficiently alleviates high-sugar-diet-induced hyperglycemia. We also observe mammalian glucagon-induced hepatic ERK peroxisomal translocation in diabetic subjects. Therefore, our results conclude that the Akh/glucagon-peroxisomal-ERK axis is a key spatial regulator of glycemic control.
Topics: Animals; Carbohydrates; Drosophila; Extracellular Signal-Regulated MAP Kinases; Glucagon; Glycemic Control; Hyperglycemia; Peroxisomes; Drosophila Proteins
PubMed: 37796662
DOI: 10.1016/j.celrep.2023.113200 -
Trends in Cell Biology Feb 2022Peroxisomes, essential subcellular organelles that fulfill important functions in lipid and reactive oxygen species metabolism, have recently emerged as key players... (Review)
Review
Peroxisomes, essential subcellular organelles that fulfill important functions in lipid and reactive oxygen species metabolism, have recently emerged as key players during viral infections. Their importance for the establishment of the cellular antiviral response has been highlighted by numerous reports of specific evasion of peroxisome-dependent signaling by different viruses. Recent data demonstrate that peroxisomes also assume important proviral functions. Here, we review and discuss the recent advances in the study of the diverse roles of peroxisomes during viral infections, from animal to plant viruses, and from basic to translational perspectives. We further discuss the future development of this emerging area and propose that peroxisome-related mechanisms represent a promising target for the development of novel antiviral strategies.
Topics: Animals; Humans; Peroxisomes; Signal Transduction; Virus Diseases
PubMed: 34696946
DOI: 10.1016/j.tcb.2021.09.010 -
Histochemistry and Cell Biology Nov 2018Peroxisomes are key metabolic organelles, which contribute to cellular lipid metabolism, e.g. the β-oxidation of fatty acids and the synthesis of myelin sheath lipids,... (Review)
Review
Peroxisomes are key metabolic organelles, which contribute to cellular lipid metabolism, e.g. the β-oxidation of fatty acids and the synthesis of myelin sheath lipids, as well as cellular redox balance. Peroxisomal dysfunction has been linked to severe metabolic disorders in man, but peroxisomes are now also recognized as protective organelles with a wider significance in human health and potential impact on a large number of globally important human diseases such as neurodegeneration, obesity, cancer, and age-related disorders. Therefore, the interest in peroxisomes and their physiological functions has significantly increased in recent years. In this review, we intend to highlight recent discoveries, advancements and trends in peroxisome research, and present an update as well as a continuation of two former review articles addressing the unsolved mysteries of this astonishing organelle. We summarize novel findings on the biological functions of peroxisomes, their biogenesis, formation, membrane dynamics and division, as well as on peroxisome-organelle contacts and cooperation. Furthermore, novel peroxisomal proteins and machineries at the peroxisomal membrane are discussed. Finally, we address recent findings on the role of peroxisomes in the brain, in neurological disorders, and in the development of cancer.
Topics: Animals; Humans; Organelles; Peroxisomes
PubMed: 30219925
DOI: 10.1007/s00418-018-1722-5 -
Current Opinion in Cell Biology Aug 2015Peroxisomes are remarkably responsive organelles. Their composition, abundance and even their mechanism of biogenesis are influenced strongly by cell type and the... (Review)
Review
Peroxisomes are remarkably responsive organelles. Their composition, abundance and even their mechanism of biogenesis are influenced strongly by cell type and the environment. This plasticity underlies peroxisomal functions in metabolism and the detoxification of dangerous reactive oxygen species. However, peroxisomes are integrated into the cellular system as a whole such that they communicate intimately with other organelles, control signaling dynamics as in the case of innate immune responses to infectious disease, and contribute to processes as fundamental as longevity. The increasing evidence for peroxisomes having roles in various cellular and organismal functions, combined with their malleability, suggests complex mechanisms operate to control cellular dynamics and the specificity of cellular responses and functions extending well beyond the peroxisome itself. A deeper understanding of the functions of peroxisomes and the mechanisms that control their plasticity could offer opportunities for exploiting changes in peroxisome abundance to control cellular function.
Topics: Animals; Humans; Immunity, Innate; Peroxisomes; Reactive Oxygen Species; Signal Transduction; Transcription, Genetic
PubMed: 26042681
DOI: 10.1016/j.ceb.2015.05.002 -
Redox Biology Oct 2023Peroxisomes are metabolically active organelles that are known for exerting oxidative metabolism, but the precise mechanism remains unclear in diabetic nephropathy (DN)....
Peroxisomes are metabolically active organelles that are known for exerting oxidative metabolism, but the precise mechanism remains unclear in diabetic nephropathy (DN). Here, we used proteomics to uncover a correlation between the antioxidant protein disulfide-bond A oxidoreductase-like protein (DsbA-L) and peroxisomal function. In vivo, renal tubular injury, oxidative stress, and cell apoptosis in high-fat diet plus streptozotocin (STZ)-induced diabetic mice were significantly increased, and these changes were accompanied by a "ghost" peroxisomal phenotype, which was further aggravated in DsbA-L-deficient diabetic mice. In vitro, the overexpression of DsbA-L in peroxisomes could improve peroxisomal phenotype and function, reduce oxidative stress and cell apoptosis induced by high glucose (HG, 30 mM) and palmitic acid (PA, 250 μM), but this effect was reversed by 3-Amino-1,2,4-triazole (3-AT, a catalase inhibitor). Mechanistically, DsbA-L regulated the activity of catalase by binding to it, thereby reducing peroxisomal leakage and proteasomal degradation of peroxisomal matrix proteins induced by HG and PA. Additionally, the expression of DsbA-L in renal tubules of patients with DN significantly decreased and was positively correlated with peroxisomal function. Taken together, these results highlight an important role of DsbA-L in ameliorating tubular injury in DN by improving peroxisomal function.
Topics: Animals; Mice; Catalase; Diabetic Nephropathies; Peroxisomes; Diabetes Mellitus, Experimental; Oxidative Stress
PubMed: 37597421
DOI: 10.1016/j.redox.2023.102855 -
Current Opinion in Microbiology Dec 2014Peroxisomes are ubiquitous organelles that harbor diverse metabolic pathways, which are essential for normal cell performance. Conserved functions of these organelles... (Review)
Review
Peroxisomes are ubiquitous organelles that harbor diverse metabolic pathways, which are essential for normal cell performance. Conserved functions of these organelles are hydrogen peroxide metabolism and β-oxidation. Cells employ multiple quality control mechanisms to ensure proper peroxisome function and to protect peroxisomes from damage. These involve the function of molecular chaperones, a peroxisomal Lon protease and autophagic removal of dysfunctional organelles. In addition, multiple mechanisms exist to combat peroxisomal oxidative stress. Here, we outline recent advances in our understanding of peroxisomal quality control, focussing on yeast and filamentous fungi.
Topics: Oxidation-Reduction; Peroxisomes; Protein Processing, Post-Translational; Signal Transduction
PubMed: 25305535
DOI: 10.1016/j.mib.2014.09.009 -
Sub-cellular Biochemistry 2018Peroxisomes and mitochondria are dynamic, multifunctional organelles that play pivotal cooperative roles in the metabolism of cellular lipids and reactive oxygen... (Review)
Review
Peroxisomes and mitochondria are dynamic, multifunctional organelles that play pivotal cooperative roles in the metabolism of cellular lipids and reactive oxygen species. Their functional interplay, the "peroxisome-mitochondria connection", also includes cooperation in anti-viral signalling and defence, as well as coordinated biogenesis by sharing key division proteins. In this review, we focus on multi-localised proteins which are shared by peroxisomes and mitochondria in mammals. We first outline the targeting and sharing of matrix proteins which are involved in metabolic cooperation. Next, we discuss shared components of peroxisomal and mitochondrial dynamics and division, and we present novel insights into the dual targeting of tail-anchored membrane proteins. Finally, we provide an overview of what is currently known about the role of shared membrane proteins in disease. What emerges is that sharing of proteins between these two organelles plays a key role in their cooperative functions which, based on new findings, may be more extensive than originally envisaged. Gaining a better insight into organelle interplay and the targeting of shared proteins is pivotal to understanding how organelle cooperation contributes to human health and disease.
Topics: Animals; Humans; Membrane Proteins; Metabolic Networks and Pathways; Mitochondria; Peroxisomes; Reactive Oxygen Species
PubMed: 30378033
DOI: 10.1007/978-981-13-2233-4_17 -
Biochimica Et Biophysica Acta May 2016This contribution describes the phenotypic differences of yeast peroxisome-deficient mutants (pex mutants). In some cases different phenotypes were reported for yeast... (Review)
Review
This contribution describes the phenotypic differences of yeast peroxisome-deficient mutants (pex mutants). In some cases different phenotypes were reported for yeast mutants deleted in the same PEX gene. These differences are most likely related to the marker proteins and methods used to detect peroxisomal remnants. This is especially evident for pex3 and pex19 mutants, where the localization of receptor docking proteins (Pex13, Pex14) resulted in the identification of peroxisomal membrane remnants, which do not contain other peroxisomal membrane proteins, such as the ring proteins Pex2, Pex10 and Pex12. These structures in pex3 and pex19 cells are the template for peroxisome formation upon introduction of the missing gene. Taken together, these data suggest that in all yeast pex mutants analyzed so far peroxisomes are not formed de novo but use membrane remnant structures as a template for peroxisome formation upon reintroduction of the missing gene. The relevance of this model for peroxisomal membrane protein and lipid sorting to peroxisomes is discussed.
Topics: Animals; Endoplasmic Reticulum; Eukaryotic Cells; Gene Expression Regulation; Humans; Membrane Proteins; Organelle Biogenesis; Peroxins; Peroxisomes; Plants; Protein Isoforms; Protein Structure, Tertiary; Protein Transport; Saccharomyces cerevisiae Proteins; Signal Transduction; Yeasts
PubMed: 26367802
DOI: 10.1016/j.bbamcr.2015.09.008