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Biochimica Et Biophysica Acta May 2016Peroxisome number and quality are maintained by its biogenesis and turnover and are important for the homeostasis of peroxisomes. Peroxisomes are increased in number by... (Review)
Review
Peroxisome number and quality are maintained by its biogenesis and turnover and are important for the homeostasis of peroxisomes. Peroxisomes are increased in number by division with dynamic morphological changes including elongation, constriction, and fission. In the course of peroxisomal division, peroxisomal morphogenesis is orchestrated by Pex11β, dynamin-like protein 1 (DLP1), and mitochondrial fission factor (Mff). Conversely, peroxisome number is reduced by its degradation. Peroxisomes are mainly degraded by pexophagy, a type of autophagy specific for peroxisomes. Upon pexophagy, an adaptor protein translocates on peroxisomal membrane and connects peroxisomes to autophagic machineries. Molecular mechanisms of pexophagy are well studied in yeast systems where several specific adaptor proteins are identified. Pexophagy in mammals also proceeds in a manner dependent on adaptor proteins. In this review, we address the recent progress in studies on peroxisome morphogenesis and pexophagy.
Topics: Animals; Dynamins; Endoplasmic Reticulum; Eukaryotic Cells; GTP Phosphohydrolases; Gene Expression Regulation; Humans; Membrane Proteins; Microtubule-Associated Proteins; Mitochondrial Proteins; Peroxins; Peroxisomes; Protein Isoforms; Protein Structure, Tertiary; Proteolysis; Saccharomyces cerevisiae Proteins; Signal Transduction; Species Specificity; Ubiquitin; Yeasts
PubMed: 26434997
DOI: 10.1016/j.bbamcr.2015.09.032 -
Journal of Integrative Plant Biology Jul 2019Plant peroxisomes are unique subcellular organelles which play an indispensable role in several key metabolic pathways, including fatty acid β-oxidation,... (Review)
Review
Plant peroxisomes are unique subcellular organelles which play an indispensable role in several key metabolic pathways, including fatty acid β-oxidation, photorespiration, and degradation of reactive oxygen species. The compartmentalization of metabolic pathways into peroxisomes is a strategy for organizing the metabolic network and improving pathway efficiency. An important prerequisite, however, is the exchange of metabolites between peroxisomes and other cell compartments. Since the first studies in the 1970s scientists contributed to understanding how solutes enter or leave this organelle. This review gives an overview about our current knowledge of the solute permeability of peroxisomal membranes described in plants, yeast, mammals and other eukaryotes. In general, peroxisomes contain in their bilayer membrane specific transporters for hydrophobic fatty acids (ABC transporter) and large cofactor molecules (carrier for ATP, NAD and CoA). Smaller solutes with molecular masses below 300-400 Da, like the organic acids malate, oxaloacetate, and 2-oxoglutarate, are shuttled via non-selective channels across the peroxisomal membrane. In comparison to yeast, human, mammals and other eukaryotes, the function of these known peroxisomal transporters and channels in plants are discussed in this review.
Topics: Fatty Acids; Membrane Transport Proteins; Oxidation-Reduction; Peroxisomes
PubMed: 30761734
DOI: 10.1111/jipb.12790 -
Trends in Biochemical Sciences Mar 2021Despite major advances in our understanding of players and mechanisms involved in peroxisome biogenesis and peroxisome degradation, very few studies have focused on... (Review)
Review
Despite major advances in our understanding of players and mechanisms involved in peroxisome biogenesis and peroxisome degradation, very few studies have focused on unraveling the multi-layered connections between, and the coordination of, these two opposing processes that regulate peroxisome homeostasis. The intersection between these processes also provides exciting avenues for future research. This review highlights the links between peroxisome biogenesis and degradation, incorporating an integrative approach that is critical not only for a mechanistic understanding, but also for manipulating the balance between these processes in relevant disease models.
Topics: Homeostasis; Metabolic Networks and Pathways; Peroxisomes
PubMed: 33046344
DOI: 10.1016/j.tibs.2020.09.006 -
Trends in Endocrinology and Metabolism:... Apr 2017Peroxisomes carry out many key functions related to lipid and reactive oxygen species (ROS) metabolism. The fundamental importance of peroxisomes for health in humans is... (Review)
Review
Peroxisomes carry out many key functions related to lipid and reactive oxygen species (ROS) metabolism. The fundamental importance of peroxisomes for health in humans is underscored by the existence of devastating genetic disorders caused by impaired peroxisomal function or lack of peroxisomes. Emerging studies suggest that peroxisomal function may also be altered with aging and contribute to the pathogenesis of a variety of diseases, including diabetes and its related complications, neurodegenerative disorders, and cancer. With increasing evidence connecting peroxisomal dysfunction to the pathogenesis of these acquired diseases, the possibility of targeting peroxisomal function in disease prevention or treatment becomes intriguing. Here, we review recent developments in understanding the pathophysiological implications of peroxisomal dysfunctions outside the context of inherited peroxisomal disorders.
Topics: Aging; Animals; Humans; Neurodegenerative Diseases; Oxidative Stress; Peroxisomes; Reactive Oxygen Species
PubMed: 28063767
DOI: 10.1016/j.tem.2016.12.003 -
Biochimica Et Biophysica Acta May 2016Peroxisomes are distinct membrane-enclosed organelles involved in the β-oxidation of fatty acids and synthesis of ether phospholipids (e.g. plasmalogens), as well as... (Review)
Review
Peroxisomes are distinct membrane-enclosed organelles involved in the β-oxidation of fatty acids and synthesis of ether phospholipids (e.g. plasmalogens), as well as cholesterol and its derivatives (e.g. bile acids). Peroxisomes comprise a distinct and highly segregated subset of cellular proteins, including those of the peroxisome membrane and the interior matrix, and while the mechanisms of protein import into peroxisomes have been extensively studied, they are not fully understood. Here we will examine the potential role of RNA trafficking and localized translation on protein import into peroxisomes and its role in peroxisome biogenesis and function. Given that RNAs encoding peroxisome biogenesis (PEX) and matrix proteins have been found in association with the endoplasmic reticulum and peroxisomes, it suggests that localized translation may play a significant role in the import pathways of these different peroxisomal constituents.
Topics: Animals; Biological Transport; Endoplasmic Reticulum; Eukaryotic Cells; Gene Expression Regulation; Humans; Membrane Proteins; Mutation; Organelle Biogenesis; Peroxisomes; Plants; Protein Isoforms; Protein Sorting Signals; RNA, Messenger; Saccharomyces cerevisiae; Saccharomyces cerevisiae Proteins; Signal Transduction
PubMed: 26367800
DOI: 10.1016/j.bbamcr.2015.09.007 -
FEBS Letters Jun 2000Peroxisome assembly in mammals requires more than 15 genes. Two isoforms of the peroxisome targeting signal type 1 (PTS1) receptor, Pex5pS and Pex5pL, are identified in... (Review)
Review
Peroxisome assembly in mammals requires more than 15 genes. Two isoforms of the peroxisome targeting signal type 1 (PTS1) receptor, Pex5pS and Pex5pL, are identified in mammals. Pex5pS and Pex5pL bind PTS1 proteins. Pex5pL, but not Pex5pS, directly interacts with the PTS2 receptor, Pex7p, carrying its cargo PTS2 protein in the cytosol. Pex5p carrying the cargos, PTS1 and PTS2, docks with the initial site Pex14p in a putative import machinery, subsequently translocating to other components such as Pex13p, Pex2p, Pex10p and Pex12p, whereby the matrix proteins are imported. The peroxins, Pex3p, Pex16p and Pex19p, function in the assembly of peroxisomal membrane vesicles that precedes the import of matrix proteins. Hence, peroxisomes may form de novo and do not have to arise from pre-existing, morphologically recognizable peroxisomes. Impaired peroxisome assembly causes peroxisome biogenesis disorders such as Zellweger syndrome.
Topics: Animals; Humans; Intracellular Membranes; Mammals; Models, Biological; Peroxisomal Disorders; Peroxisomal Targeting Signal 2 Receptor; Peroxisome-Targeting Signal 1 Receptor; Peroxisomes; Receptors, Cytoplasmic and Nuclear
PubMed: 10878247
DOI: 10.1016/s0014-5793(00)01667-7 -
IUBMB Life Jul 2009Peroxisomes play an important role in lipid metabolic pathways and are implicated in many human disorders. Their biogenesis has been studied over the last two decades... (Review)
Review
Peroxisomes play an important role in lipid metabolic pathways and are implicated in many human disorders. Their biogenesis has been studied over the last two decades using many uni and multi-cellular model systems and many aspects of the mechanisms and proteins involved in peroxisome biogenesis are conserved from yeast to humans. In this manuscript we review the recent progress made in our understanding of the mechanisms by which matrix and membrane proteins are sorted to and assembled into peroxisomes.
Topics: Cytosol; Endoplasmic Reticulum; Humans; Intracellular Membranes; Membrane Proteins; Peroxisomal Targeting Signal 2 Receptor; Peroxisome-Targeting Signal 1 Receptor; Peroxisomes; Receptors, Cytoplasmic and Nuclear
PubMed: 19455563
DOI: 10.1002/iub.196 -
Biochimica Et Biophysica Acta May 2016Peroxisomes are ubiquitous organelles of eukaryotic cells, and it is becoming increasingly clear that the biogenesis of these multi-purpose organelles is more complex... (Review)
Review
Peroxisomes are ubiquitous organelles of eukaryotic cells, and it is becoming increasingly clear that the biogenesis of these multi-purpose organelles is more complex than initially anticipated. Along this line, peroxisomes exhibit features, which clearly distinguish them from other cellular organelles, like their ability to import folded proteins or their capability to form de novo. However, further insight into the cellular life of peroxisomes also revealed features that they share with other organelles, such as organelle fission or regulated degradation by autophagy, that are similar for peroxisomes, mitochondria and chloroplasts. This special issue highlights recent progress in the understanding of the biogenesis of peroxisomes with emphasis on the assembly, maintenance and dynamics of the organelles. In particular, it focuses on the following areas: (i) topogenesis of peroxisomal matrix proteins as well as the structure and function of peroxisomal protein import machineries. (ii) Peroxisomal targeting of membrane proteins and de novo formation of peroxisomes. (iii) Maintenance of peroxisomes in health and disease. (iv) Proliferation and regulated degradation of peroxisomes. (v) Motility and inheritance of peroxisomes. (vi) Role of peroxisomes in the cellular context.
Topics: Animals; Autophagy; Eukaryotic Cells; Humans; Intracellular Membranes; Membrane Fusion; Membrane Proteins; Organelle Biogenesis; Peroxisomes; Protein Transport
PubMed: 26851075
DOI: 10.1016/j.bbamcr.2016.01.020 -
Cell Cycle (Georgetown, Tex.) 2017Peroxisomes are essential and dynamic organelles that allow cells to rapidly adapt and cope with changing environments and/or physiological conditions by modulation of... (Review)
Review
Peroxisomes are essential and dynamic organelles that allow cells to rapidly adapt and cope with changing environments and/or physiological conditions by modulation of both peroxisome biogenesis and turnover. Peroxisome biogenesis involves the assembly of peroxisome membranes and the import of peroxisomal matrix proteins. The latter depends on the receptor, PEX5, which recognizes peroxisomal matrix proteins in the cytosol directly or indirectly, and transports them to the peroxisomal lumen. In this review, we discuss the role of PEX5 ubiquitination in both peroxisome biogenesis and turnover, specifically in PEX5 receptor recycling, stability and abundance, as well as its role in pexophagy (autophagic degradation of peroxisomes).
Topics: Animals; Autophagy; Homeostasis; Humans; Peroxisome-Targeting Signal 1 Receptor; Peroxisomes; Receptors, Cytoplasmic and Nuclear; Ubiquitination
PubMed: 28933989
DOI: 10.1080/15384101.2017.1376149 -
Biochimica Et Biophysica Acta May 2016Peroxisomes contain numerous enzymatic activities that are important for mammalian physiology. Patients lacking either all peroxisomal functions or a single enzyme or... (Review)
Review
Peroxisomes contain numerous enzymatic activities that are important for mammalian physiology. Patients lacking either all peroxisomal functions or a single enzyme or transporter function typically develop severe neurological deficits, which originate from aberrant development of the brain, demyelination and loss of axonal integrity, neuroinflammation or other neurodegenerative processes. Whilst correlating peroxisomal properties with a compilation of pathologies observed in human patients and mouse models lacking all or individual peroxisomal functions, we discuss the importance of peroxisomal metabolites and tissue- and cell type-specific contributions to the observed brain pathologies. This enables us to deconstruct the local and systemic contribution of individual metabolic pathways to specific brain functions. We also review the recently discovered variability of pathological symptoms in cases with unexpectedly mild presentation of peroxisome biogenesis disorders. Finally, we explore the emerging evidence linking peroxisomes to more common neurological disorders such as Alzheimer's disease, autism and amyotrophic lateral sclerosis.
Topics: ATPases Associated with Diverse Cellular Activities; Animals; Brain; Disease Models, Animal; Gene Expression Regulation; Humans; Membrane Proteins; Metabolic Networks and Pathways; Mice; Mutation; Peroxisomal Disorders; Peroxisomes; Protein Isoforms; Protein Transport; Synaptic Transmission
PubMed: 26686055
DOI: 10.1016/j.bbamcr.2015.12.005