-
Journal of Cell Science May 2020Peroxisomes are single-membrane organelles present in eukaryotes. The functional importance of peroxisomes in humans is represented by peroxisome-deficient peroxisome... (Review)
Review
Peroxisomes are single-membrane organelles present in eukaryotes. The functional importance of peroxisomes in humans is represented by peroxisome-deficient peroxisome biogenesis disorders (PBDs), including Zellweger syndrome. Defects in the genes that encode the 14 peroxins that are required for peroxisomal membrane assembly, matrix protein import and division have been identified in PBDs. A number of recent findings have advanced our understanding of the biology, physiology and consequences of functional defects in peroxisomes. In this Review, we discuss a cooperative cell defense mechanisms against oxidative stress that involves the localization of BAK (also known as BAK1) to peroxisomes, which alters peroxisomal membrane permeability, resulting in the export of catalase, a peroxisomal enzyme. Another important recent finding is the discovery of a nucleoside diphosphate kinase-like protein that has been shown to be essential for how the energy GTP is generated and provided for the fission of peroxisomes. With regard to PBDs, we newly identified a mild mutation, Pex26-F51L that causes only hearing loss. We will also discuss findings from a new PBD model mouse defective in Pex14, which manifested dysregulation of the BDNF-TrkB pathway, an essential signaling pathway in cerebellar morphogenesis. Here, we thus aim to provide a current view of peroxisome biogenesis and the molecular pathogenesis of PBDs.
Topics: Animals; Intracellular Membranes; Mice; Peroxins; Peroxisomal Disorders; Peroxisomes; Protein Transport
PubMed: 32393673
DOI: 10.1242/jcs.236943 -
Proceedings of the Japan Academy.... 2016Peroxisome is a single-membrane-bounded ubiquitous organelle containing a hundred different enzymes that catalyze various metabolic pathways such as β-oxidation of very... (Review)
Review
Peroxisome is a single-membrane-bounded ubiquitous organelle containing a hundred different enzymes that catalyze various metabolic pathways such as β-oxidation of very long-chain fatty acids and synthesis of plasmalogens. To investigate peroxisome biogenesis and human peroxisome biogenesis disorders (PBDs) including Zellweger syndrome, more than a dozen different complementation groups of Chinese hamster ovary (CHO) cell mutants impaired in peroxisome biogenesis are isolated as a model experimental system. By taking advantage of rapid functional complementation assay of the CHO cell mutants, successful cloning of PEX genes encoding peroxins required for peroxisome assembly invaluably contributed to the accomplishment of cloning of pathogenic genes responsible for PBDs. Peroxins are divided into three groups: 1) peroxins including Pex3p, Pex16p and Pex19p, are responsible for peroxisome membrane biogenesis via Pex19p- and Pex3p-dependent class I and Pex19p- and Pex16p-dependent class II pathways; 2) peroxins that function in matrix protein import; 3) those such as Pex11pβ are involved in peroxisome division where DLP1, Mff, and Fis1 coordinately function.
Topics: Animals; CHO Cells; Cricetinae; Cricetulus; Humans; Peroxisomal Disorders; Peroxisomes
PubMed: 27941306
DOI: 10.2183/pjab.92.463 -
Biochimica Et Biophysica Acta May 2016Peroxisomes proliferate by growth and division of pre-existing peroxisomes or could arise de novo. Though the de novo pathway of peroxisome biogenesis is a more recent... (Review)
Review
Peroxisomes proliferate by growth and division of pre-existing peroxisomes or could arise de novo. Though the de novo pathway of peroxisome biogenesis is a more recent discovery, several studies have highlighted key mechanistic details of the pathway. The endoplasmic reticulum (ER) is the primary source of lipids and proteins for the newly-formed peroxisomes. More recently, an intricate sorting process functioning at the ER has been proposed, that segregates specific PMPs first to peroxisome-specific ER domains (pER) and then assembles PMPs selectively into distinct pre-peroxisomal vesicles (ppVs) that later fuse to form import-competent peroxisomes. In addition, plausible roles of the three key peroxins Pex3, Pex16 and Pex19, which are also central to the growth and division pathway, have been suggested in the de novo process. In this review, we discuss key developments and highlight the unexplored avenues in de novo peroxisome biogenesis.
Topics: Animals; Endoplasmic Reticulum; Eukaryotic Cells; Fungal Proteins; 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: 26381541
DOI: 10.1016/j.bbamcr.2015.09.014 -
Current Opinion in Cell Biology Apr 2016Peroxisomes participate in lipid metabolism, and are a major source of ROS in the cell. Their importance in cellular energy balance and redox homeostasis is... (Review)
Review
Peroxisomes participate in lipid metabolism, and are a major source of ROS in the cell. Their importance in cellular energy balance and redox homeostasis is well-established, as is the need to maintain peroxisome homeostasis to prevent pathologies associated with too few, or too many, of these organelles. How cells regulate peroxisome number has remained somewhat elusive. Recently, the tumor suppressors ATM and TSC, which regulate mTORC1 signaling, have been localized to peroxisomes. When activated by peroxisomal ROS, ATM signals to TSC to repress mTORC1 signaling and increase autophagic flux in cells, and also phosphorylates the peroxisomal protein PEX 5 to target peroxisomes for selective autophagy (pexophagy), providing a mechanism for regulation of peroxisomal homeostasis using ROS as a rheostat.
Topics: Animals; Autophagy; Homeostasis; Humans; Organelles; Peroxisomes; Signal Transduction
PubMed: 26967755
DOI: 10.1016/j.ceb.2016.02.017 -
Current Opinion in Cell Biology Feb 2018Peroxisome biogenesis is governed by molecular machineries, which are either unique to peroxisomes or are partially shared with mitochondria. As peroxisomes have... (Review)
Review
Peroxisome biogenesis is governed by molecular machineries, which are either unique to peroxisomes or are partially shared with mitochondria. As peroxisomes have important protective functions in the cell, modulation of their number is important for human health and disease. Significant progress has been made towards our understanding of the mechanisms of peroxisome formation, revealing a remarkable plasticity of the peroxisome biogenesis pathway. Here we discuss most recent findings with particular focus on peroxisome formation in mammalian cells.
Topics: Animals; Humans; Intracellular Membranes; Metabolic Networks and Pathways; Mitochondria; Organelle Biogenesis; Peroxisomes
PubMed: 29475136
DOI: 10.1016/j.ceb.2018.02.002 -
Histochemistry and Cell Biology May 2012Peroxisomes contribute to several crucial metabolic processes such as β-oxidation of fatty acids, biosynthesis of ether phospholipids and metabolism of reactive oxygen... (Review)
Review
Peroxisomes contribute to several crucial metabolic processes such as β-oxidation of fatty acids, biosynthesis of ether phospholipids and metabolism of reactive oxygen species, which render them indispensable to human health and development. Peroxisomes are highly dynamic organelles that rapidly assemble, multiply and degrade in response to metabolic needs. In recent years, the interest in peroxisomes and their physiological functions has significantly increased. This review intends to highlight recent discoveries and trends in peroxisome research, and represents an update as well as a continuation of a former review article. Novel exciting findings on the biological functions, biogenesis, formation and degradation of peroxisomes, on peroxisomal dynamics and division, as well as on the interaction and cross-talk of peroxisomes with other subcellular compartments are addressed. Furthermore, recent findings on the role of peroxisomes in the brain are discussed.
Topics: Animals; Fatty Acids; Humans; Models, Biological; Peroxisomes; Phospholipids; Reactive Oxygen Species
PubMed: 22415027
DOI: 10.1007/s00418-012-0941-4 -
Traffic (Copenhagen, Denmark) Mar 2011The essential role of peroxisomes in fatty acid oxidation, anaplerotic metabolism, and hydrogen peroxide turnover is well established. Recent findings suggest that these... (Review)
Review
The essential role of peroxisomes in fatty acid oxidation, anaplerotic metabolism, and hydrogen peroxide turnover is well established. Recent findings suggest that these and other related biochemical processes governed by the organelle may also play a critical role in regulating cellular aging. The goal of this review is to summarize and integrate into a model the evidence that peroxisome metabolism actually helps define the replicative and chronological age of a eukaryotic cell. In this model, peroxisomal reactive oxygen species (ROS) are seen as altering organelle biogenesis and function, and eliciting changes in the dynamic communication networks that exist between peroxisomes and other cellular compartments. At low levels, peroxisomal ROS activate an anti-aging program in the cell; at concentrations beyond a specific threshold, a pro-aging course is triggered.
Topics: Animals; Cellular Senescence; Fatty Acids; Humans; Peroxisomes; Signal Transduction
PubMed: 21083858
DOI: 10.1111/j.1600-0854.2010.01144.x -
Microscopy Research and Technique Jun 2003Peroxisomes are essential organelles that may be involved in various functions, dependent on organism, cell type, developmental stage of the cell, and the environment.... (Review)
Review
Peroxisomes are essential organelles that may be involved in various functions, dependent on organism, cell type, developmental stage of the cell, and the environment. Until recently, peroxisomes were viewed as a class of static organelles that developed by growth and fission from pre-existing organelles. Recent observations have challenged this view by providing evidence that peroxisomes may be part of the endomembrane system and constitute a highly dynamic population of organelles that arises and is removed upon environmental demands. Additionally, evidence is now accumulating that peroxisomes may arise by alternative methods. This review summarizes relevant recent data on this subject. In addition, the progress in the understanding of the principles of the peroxisomal matrix protein import machinery is discussed.
Topics: PHEX Phosphate Regulating Neutral Endopeptidase; Peroxisomes; Proteins; Yeasts
PubMed: 12740820
DOI: 10.1002/jemt.10323 -
Journal of Cellular and Molecular... 2003Peroxisomes are metabolic organelles with enzymatic content that are found in virtually all cells and are involved in beta-oxidation of fatty acids, hydrogen... (Review)
Review
Peroxisomes are metabolic organelles with enzymatic content that are found in virtually all cells and are involved in beta-oxidation of fatty acids, hydrogen peroxide-based respiration and defence against oxidative stress. The steps of their biogenesis involves "peroxins", proteins encoded by PEX genes. Peroxins are involved in three key stages of peroxisome development: (1). import of peroxisomal membrane proteins; (2). import of peroxisomal matrix proteins and (3). peroxisome proliferation. Of these three areas, peroxisomal matrix-protein import is by far the best understood and accounts for most of the available published data on peroxisome biogenesis. Defects in peroxisome biogenesis result in peroxisome biogenesis disorders (PBDs), which although rare, have no known cure to-date. This review explores current understanding of each key area in peroxisome biogenesis, paying particular attention to the role of protein import.
Topics: Animals; Biological Transport, Active; Humans; Membrane Proteins; Peroxisomes; Plants; Proteins; Saccharomyces cerevisiae
PubMed: 14754507
DOI: 10.1111/j.1582-4934.2003.tb00241.x -
Clinical Chemistry and Laboratory... Jun 2001One of the most rapidly developing areas of organelle biology, which has a major involvement in biochemical pharmacology, is the research into the peroxisomal function.... (Review)
Review
One of the most rapidly developing areas of organelle biology, which has a major involvement in biochemical pharmacology, is the research into the peroxisomal function. There is a large group of compounds that are capable of inducing liver enlargement, proliferation of peroxisomal structures, and induction of peroxisomal and extraperoxisomal fatty acid-oxidizing enzymes in rodent liver, called peroxisome proliferators. This list includes hypolipidemic drugs, analgesics, uricosuric drugs, environmental pollutants, phthalates, etc. Some peroxisome proliferators have also been shown to increase the incidence of liver tumors. This review describes the characteristics of peroxisome proliferation in rodent liver and gives examples of different classes of chemicals that produce this effect. Mechanisms of initiation of peroxisome proliferation in rodent hepatocytes, including peroxisome proliferator-activated receptors, are also described. Rodent peroxisome proliferators are not considered to be genotoxic agents. Proposed mechanisms of liver tumor formation include induction of sustained oxidative stress, enhanced cell replication, promotion of spontaneous preneoplastic lesions, and inhibition of apoptosis. In addition, the absence of effects of peroxisome proliferators on peroxisome proliferator-associated parameters supports the hypothesis that human liver cells are refractory to peroxisome proliferator-induced hepatic carcinogenesis.
Topics: Animals; Carcinogens; Cell Division; Cocarcinogenesis; Humans; Liver; Liver Neoplasms, Experimental; Mice; Models, Biological; Oxidative Stress; Peroxisome Proliferators; Peroxisomes; Rats; Species Specificity
PubMed: 11506454
DOI: 10.1515/CCLM.2001.076