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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 -
Trends in Cell Biology Jan 2023Peroxisomes are essential metabolic organelles, well known for their roles in the metabolism of complex lipids and reactive ionic species. In the past 10 years,... (Review)
Review
Peroxisomes are essential metabolic organelles, well known for their roles in the metabolism of complex lipids and reactive ionic species. In the past 10 years, peroxisomes have also been cast as central regulators of immunity. Lipid metabolites of peroxisomes, such as polyunsaturated fatty acids (PUFAs), are precursors for important immune mediators, including leukotrienes (LTs) and resolvins. Peroxisomal redox metabolism modulates cellular immune signaling such as nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) activation. Additionally, peroxisomal β-oxidation and ether lipid synthesis control the development and aspects of the activation of both innate and adaptive immune cells. Finally, peroxisome number and metabolic activity have been linked to inflammatory diseases. These discoveries have opened avenues of investigation aimed at targeting peroxisomes for therapeutic intervention in immune disorders, inflammation, and cancer.
Topics: Humans; Peroxisomes; Fatty Acids; Oxidation-Reduction; Neoplasms; Inflammation
PubMed: 35788297
DOI: 10.1016/j.tcb.2022.06.001 -
Nature May 2023Peroxisomes are organelles that carry out β-oxidation of fatty acids and amino acids. Both rare and prevalent diseases are caused by their dysfunction. Among...
Peroxisomes are organelles that carry out β-oxidation of fatty acids and amino acids. Both rare and prevalent diseases are caused by their dysfunction. Among disease-causing variant genes are those required for protein transport into peroxisomes. The peroxisomal protein import machinery, which also shares similarities with chloroplasts, is unique in transporting folded and large, up to 10 nm in diameter, protein complexes into peroxisomes. Current models postulate a large pore formed by transmembrane proteins; however, so far, no pore structure has been observed. In the budding yeast Saccharomyces cerevisiae, the minimum transport machinery includes the membrane proteins Pex13 and Pex14 and the cargo-protein-binding transport receptor, Pex5. Here we show that Pex13 undergoes liquid-liquid phase separation (LLPS) with Pex5-cargo. Intrinsically disordered regions in Pex13 and Pex5 resemble those found in nuclear pore complex proteins. Peroxisomal protein import depends on both the number and pattern of aromatic residues in these intrinsically disordered regions, consistent with their roles as 'stickers' in associative polymer models of LLPS. Finally, imaging fluorescence cross-correlation spectroscopy shows that cargo import correlates with transient focusing of GFP-Pex13 and GFP-Pex14 on the peroxisome membrane. Pex13 and Pex14 form foci in distinct time frames, suggesting that they may form channels at different saturating concentrations of Pex5-cargo. Our findings lead us to suggest a model in which LLPS of Pex5-cargo with Pex13 and Pex14 results in transient protein transport channels.
Topics: Intracellular Membranes; Membrane Proteins; Peroxins; Peroxisome-Targeting Signal 1 Receptor; Peroxisomes; Phase Transition; Protein Binding; Protein Transport; Saccharomyces cerevisiae; Saccharomyces cerevisiae Proteins; Intrinsically Disordered Proteins
PubMed: 37165185
DOI: 10.1038/s41586-023-06044-1 -
Physiological Reviews Jan 2023Peroxisomes are subcellular organelles that play a central role in human physiology by catalyzing a range of unique metabolic functions. The importance of peroxisomes... (Review)
Review
Peroxisomes are subcellular organelles that play a central role in human physiology by catalyzing a range of unique metabolic functions. The importance of peroxisomes for human health is exemplified by the existence of a group of usually severe diseases caused by an impairment in one or more peroxisomal functions. Among others these include the Zellweger spectrum disorders, X-linked adrenoleukodystrophy, and Refsum disease. To fulfill their role in metabolism, peroxisomes require continued interaction with other subcellular organelles including lipid droplets, lysosomes, the endoplasmic reticulum, and mitochondria. In recent years it has become clear that the metabolic alliance between peroxisomes and other organelles requires the active participation of tethering proteins to bring the organelles physically closer together, thereby achieving efficient transfer of metabolites. This review intends to describe the current state of knowledge about the metabolic role of peroxisomes in humans, with particular emphasis on the metabolic partnership between peroxisomes and other organelles and the consequences of genetic defects in these processes. We also describe the biogenesis of peroxisomes and the consequences of the multiple genetic defects therein. In addition, we discuss the functional role of peroxisomes in different organs and tissues and include relevant information derived from model systems, notably peroxisomal mouse models. Finally, we pay particular attention to a hitherto underrated role of peroxisomes in viral infections.
Topics: Animals; Humans; Mice; Peroxisomes
PubMed: 35951481
DOI: 10.1152/physrev.00051.2021 -
Cell Metabolism Jan 2024Mitochondria are central hubs of cellular metabolism and are tightly connected to signaling pathways. The dynamic plasticity of mitochondria to fuse, divide, and contact... (Review)
Review
Mitochondria are central hubs of cellular metabolism and are tightly connected to signaling pathways. The dynamic plasticity of mitochondria to fuse, divide, and contact other organelles to flux metabolites is central to their function. To ensure bona fide functionality and signaling interconnectivity, diverse molecular mechanisms evolved. An ancient and long-overlooked mechanism is the generation of mitochondrial-derived vesicles (MDVs) that shuttle selected mitochondrial cargoes to target organelles. Just recently, we gained significant insight into the mechanisms and functions of MDV transport, ranging from their role in mitochondrial quality control to immune signaling, thus demonstrating unexpected and diverse physiological aspects of MDV transport. This review highlights the origin of MDVs, their biogenesis, and their cargo selection, with a specific focus on the contribution of MDV transport to signaling across cell and organ barriers. Additionally, the implications of MDVs in peroxisome biogenesis, neurodegeneration, metabolism, aging, and cancer are discussed.
Topics: Mitochondria; Peroxisomes; Biological Transport
PubMed: 38171335
DOI: 10.1016/j.cmet.2023.11.014 -
Redox Biology Nov 2023Despite intensive research on peroxisome biochemistry, the role of glutathione in peroxisomal redox homeostasis has remained a matter of speculation for many years, and... (Review)
Review
Despite intensive research on peroxisome biochemistry, the role of glutathione in peroxisomal redox homeostasis has remained a matter of speculation for many years, and only recently has this issue started to be experimentally addressed. Here, we summarize and compare data from several organisms on the peroxisome-glutathione topic. It is clear from this comparison that the repertoire of glutathione-utilizing enzymes in peroxisomes of different organisms varies widely. In addition, the available data suggest that the kinetic connectivity between the cytosolic and peroxisomal pools of glutathione may also be different in different organisms, with some possessing a peroxisomal membrane that is promptly permeable to glutathione whereas in others this may not be the case. However, regardless of the differences, the picture that emerges from all these data is that glutathione is a crucial component of the antioxidative system that operates inside peroxisomes in all organisms.
Topics: Peroxisomes; Glutathione; Antioxidants; Oxidation-Reduction; Homeostasis
PubMed: 37804696
DOI: 10.1016/j.redox.2023.102917 -
Advances in Experimental Medicine and... 2020Peroxisomes 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... (Review)
Review
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. Several new mutations in peroxins from patients with mild PBD phenotype or patients with phenotypes unrelated to the commonly observed impairments of PBD patients are found by next-generation sequencing. Exploring a dysfunctional step(s) caused by the mutation is important for unveiling the pathogenesis of novel mutation by means of cellular and biochemical analyses.
Topics: Humans; Mutation; Peroxisomal Disorders; Peroxisomes; Phenotype
PubMed: 33417206
DOI: 10.1007/978-3-030-60204-8_4 -
The Journal of Clinical Investigation Feb 2019Peroxisomes perform essential functions in lipid metabolism, including fatty acid oxidation and plasmalogen synthesis. Here, we describe a role for peroxisomal lipid...
Peroxisomes perform essential functions in lipid metabolism, including fatty acid oxidation and plasmalogen synthesis. Here, we describe a role for peroxisomal lipid metabolism in mitochondrial dynamics in brown and beige adipocytes. Adipose tissue peroxisomal biogenesis was induced in response to cold exposure through activation of the thermogenic coregulator PRDM16. Adipose-specific knockout of the peroxisomal biogenesis factor Pex16 (Pex16-AKO) in mice impaired cold tolerance, decreased energy expenditure, and increased diet-induced obesity. Pex16 deficiency blocked cold-induced mitochondrial fission, decreased mitochondrial copy number, and caused mitochondrial dysfunction. Adipose-specific knockout of the peroxisomal β-oxidation enzyme acyl-CoA oxidase 1 (Acox1-AKO) was not sufficient to affect adiposity, thermogenesis, or mitochondrial copy number, but knockdown of the plasmalogen synthetic enzyme glyceronephosphate O-acyltransferase (GNPAT) recapitulated the effects of Pex16 inactivation on mitochondrial morphology and function. Plasmalogens are present in mitochondria and decreased with Pex16 inactivation. Dietary supplementation with plasmalogens increased mitochondrial copy number, improved mitochondrial function, and rescued thermogenesis in Pex16-AKO mice. These findings support a surprising interaction between peroxisomes and mitochondria regulating mitochondrial dynamics and thermogenesis.
Topics: Acyl-CoA Oxidase; Adipose Tissue; Animals; COS Cells; Chlorocebus aethiops; Cold Temperature; HEK293 Cells; Humans; Lipids; Mice; Mice, Knockout; Mitochondria; Mitochondrial Dynamics; Peroxins; Peroxisomes; Plasmalogens; Thermogenesis
PubMed: 30511960
DOI: 10.1172/JCI120606 -
Sub-cellular Biochemistry 2018Plant peroxisomes are required for a number of fundamental physiological processes, such as primary and secondary metabolism, development and stress response. Indexing... (Review)
Review
Plant peroxisomes are required for a number of fundamental physiological processes, such as primary and secondary metabolism, development and stress response. Indexing the dynamic peroxisome proteome is prerequisite to fully understanding the importance of these organelles. Mass Spectrometry (MS)-based proteome analysis has allowed the identification of novel peroxisomal proteins and pathways in a relatively high-throughput fashion and significantly expanded the list of proteins and biochemical reactions in plant peroxisomes. In this chapter, we summarize the experimental proteomic studies performed in plants, compile a list of ~200 confirmed Arabidopsis peroxisomal proteins, and discuss the diverse plant peroxisome functions with an emphasis on the role of Arabidopsis MS-based proteomics in discovering new peroxisome functions. Many plant peroxisome proteins and biochemical pathways are specific to plants, substantiating the complexity, plasticity and uniqueness of plant peroxisomes. Mapping the full plant peroxisome proteome will provide a knowledge base for the improvement of crop production, quality and stress tolerance.
Topics: Arabidopsis; Arabidopsis Proteins; Peroxisomes; Plant Cells; Proteome; Proteomics
PubMed: 30378017
DOI: 10.1007/978-981-13-2233-4_1 -
Biomolecules Aug 2020Peroxisomes are eukaryotic organelles that are essential for growth and development. They are highly metabolically active and house many biochemical reactions, including... (Review)
Review
Peroxisomes are eukaryotic organelles that are essential for growth and development. They are highly metabolically active and house many biochemical reactions, including lipid metabolism and synthesis of signaling molecules. Most of these metabolic pathways are shared with other compartments, such as Endoplasmic reticulum (ER), mitochondria, and plastids. Peroxisomes, in common with all other cellular organelles are dependent on a wide range of cofactors, such as adenosine 5'-triphosphate (ATP), Coenzyme A (CoA), and nicotinamide adenine dinucleotide (NAD). The availability of the peroxisomal cofactor pool controls peroxisome function. The levels of these cofactors available for peroxisomal metabolism is determined by the balance between synthesis, import, export, binding, and degradation. Since the final steps of cofactor synthesis are thought to be located in the cytosol, cofactors must be imported into peroxisomes. This review gives an overview about our current knowledge of the permeability of the peroxisomal membrane with the focus on ATP, CoA, and NAD. Several members of the mitochondrial carrier family are located in peroxisomes, catalyzing the transfer of these organic cofactors across the peroxisomal membrane. Most of the functions of these peroxisomal cofactor transporters are known from studies in yeast, humans, and plants. Parallels and differences between the transporters in the different organisms are discussed here.
Topics: Adenosine Triphosphate; Biological Transport; Coenzyme A; Humans; NAD; Peroxisomes; Plants; Yeasts
PubMed: 32806597
DOI: 10.3390/biom10081174