-
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 -
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 -
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 -
Cells May 2021Peroxisomes play essential roles in diverse cellular metabolism functions, and their dynamic homeostasis is maintained through the coordination of peroxisome biogenesis... (Review)
Review
Peroxisomes play essential roles in diverse cellular metabolism functions, and their dynamic homeostasis is maintained through the coordination of peroxisome biogenesis and turnover. Pexophagy, selective autophagic degradation of peroxisomes, is a major mechanism for removing damaged and/or superfluous peroxisomes. Dysregulation of pexophagy impairs the physiological functions of peroxisomes and contributes to the progression of many human diseases. However, the mechanisms and functions of pexophagy in mammalian cells remain largely unknown compared to those in yeast. This review focuses on mammalian pexophagy and aims to advance the understanding of the roles of pexophagy in human health and diseases. Increasing evidence shows that ubiquitination can serve as a signal for pexophagy, and ubiquitin-binding receptors, substrates, and E3 ligases/deubiquitinases involved in pexophagy have been described. Alternatively, pexophagy can be achieved in a ubiquitin-independent manner. We discuss the mechanisms of these ubiquitin-dependent and ubiquitin-independent pexophagy pathways and summarize several inducible conditions currently used to study pexophagy. We highlight several roles of pexophagy in human health and how its dysregulation may contribute to diseases.
Topics: Animals; Humans; Macroautophagy; Peroxisomes; Signal Transduction; Ubiquitination
PubMed: 34063724
DOI: 10.3390/cells10051094 -
Biochimica Et Biophysica Acta May 2016Mutations in the PEX1 gene, which encodes a protein required for peroxisome biogenesis, are the most common cause of the Zellweger spectrum diseases. The recognition... (Review)
Review
Mutations in the PEX1 gene, which encodes a protein required for peroxisome biogenesis, are the most common cause of the Zellweger spectrum diseases. The recognition that Pex1p shares a conserved ATP-binding domain with p97 and NSF led to the discovery of the extended family of AAA+-type ATPases. So far, four AAA+-type ATPases are related to peroxisome function. Pex6p functions together with Pex1p in peroxisome biogenesis, ATAD1/Msp1p plays a role in membrane protein targeting and a member of the Lon-family of proteases is associated with peroxisomal quality control. This review summarizes the current knowledge on the AAA+-proteins involved in peroxisome biogenesis and function.
Topics: ATPases Associated with Diverse Cellular Activities; Adenosine Triphosphatases; Animals; Eukaryotic Cells; Gene Expression Regulation; Humans; Membrane Proteins; Organelle Biogenesis; Peroxisomes; Plants; Protein Isoforms; Protein Structure, Secondary; Protein Structure, Tertiary; Protein Transport; Saccharomyces cerevisiae; Saccharomyces cerevisiae Proteins; Signal Transduction
PubMed: 26453804
DOI: 10.1016/j.bbamcr.2015.10.001 -
Journal of Cell Science Jun 2023Membrane contact sites are defined as regions of close proximity between two membranes; this association is mediated by protein-protein and/or protein-lipid... (Review)
Review
Membrane contact sites are defined as regions of close proximity between two membranes; this association is mediated by protein-protein and/or protein-lipid interactions. Contact sites are often involved in lipid transport, but also can perform other functions. Peroxisomal membrane contact sites have obtained little attention compared to those of other cell organelles. However, recent studies resulted in a big leap in our knowledge of the occurrence, composition and function of peroxisomal contact sites. Studies in yeast strongly contributed to this progress. In this Review, we present an overview of our current knowledge on peroxisomal membrane contact sites in various yeast species, including Hansenula polymorpha, Saccharomyces cerevisiae, Pichia pastoris and Yarrowia lipolytica. Yeast peroxisomes form contacts with almost all other cellular organelles and with the plasma membrane. The absence of a component of a yeast peroxisomal contact site complex results in a range of peroxisomal phenotypes, including metabolic and biogenesis defects and alterations in organelle number, size or position.
Topics: Saccharomyces cerevisiae; Peroxisomes; Mitochondrial Membranes; Biological Transport; Lipids; Fungal Proteins; Saccharomyces cerevisiae Proteins
PubMed: 37288671
DOI: 10.1242/jcs.259440 -
Molecular and Biochemical Parasitology 2016Representatives of all major lineages of eukaryotes contain peroxisomes with similar morphology and mode of biogenesis, indicating a monophyletic origin of the... (Review)
Review
Representatives of all major lineages of eukaryotes contain peroxisomes with similar morphology and mode of biogenesis, indicating a monophyletic origin of the organelles within the common ancestor of all eukaryotes. Peroxisomes originated from the endoplasmic reticulum, but despite a common origin and shared morphological features, peroxisomes from different organisms show a remarkable diversity of enzyme content and the metabolic processes present can vary dependent on nutritional or developmental conditions. A common characteristic and probable evolutionary driver for the origin of the organelle is an involvement in lipid metabolism, notably HO-dependent fatty-acid oxidation. Subsequent evolution of the organelle in different lineages involved multiple acquisitions of metabolic processes-often involving retargeting enzymes from other cell compartments-and losses. Information about peroxisomes in protists is still scarce, but available evidence, including new bioinformatics data reported here, indicate striking diversity amongst free-living and parasitic protists from different phylogenetic supergroups. Peroxisomes in only some protists show major involvement in HO-dependent metabolism, as in peroxisomes of mammalian, plant and fungal cells. Compartmentalization of glycolytic and gluconeogenic enzymes inside peroxisomes is characteristic of kinetoplastids and diplonemids, where the organelles are hence called glycosomes, whereas several other excavate parasites (Giardia, Trichomonas) have lost peroxisomes. Amongst alveolates and amoebozoans patterns of peroxisome loss are more complicated. Often, a link is apparent between the niches occupied by the parasitic protists, nutrient availability, and the absence of the organelles or their presence with a specific enzymatic content. In trypanosomatids, essentiality of peroxisomes may be considered for use in anti-parasite drug discovery.
Topics: Animals; Biological Evolution; Energy Metabolism; Oxidation-Reduction; Parasites; Peroxisomes
PubMed: 26896770
DOI: 10.1016/j.molbiopara.2016.02.005 -
Plant Physiology Jan 2018Recent advances highlight understanding of the diversity of peroxisome contributions to plant biology and the mechanisms through which these essential organelles are... (Review)
Review
Recent advances highlight understanding of the diversity of peroxisome contributions to plant biology and the mechanisms through which these essential organelles are generated.
Topics: Autophagy; Models, Biological; Organelle Biogenesis; Peroxisomes; Plants; Ubiquitination
PubMed: 29021223
DOI: 10.1104/pp.17.01050 -
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 -
Experimental & Molecular Medicine Sep 2020In recent decades, the role of the peroxisome in physiology and disease conditions has become increasingly important. Together with the mitochondria and other cellular... (Review)
Review
In recent decades, the role of the peroxisome in physiology and disease conditions has become increasingly important. Together with the mitochondria and other cellular organelles, peroxisomes support key metabolic platforms for the oxidation of various fatty acids and regulate redox conditions. In addition, peroxisomes contribute to the biosynthesis of essential lipid molecules, such as bile acid, cholesterol, docosahexaenoic acid, and plasmalogen. Therefore, the quality control mechanisms that regulate peroxisome biogenesis and degradation are important for cellular homeostasis. Current evidence indicates that peroxisomal function is often reduced or dysregulated in various human disease conditions, such as neurodegenerative diseases. Here, we review the recent progress that has been made toward understanding the quality control systems that regulate peroxisomes and their pathological implications.
Topics: Animals; Biomarkers; Disease Susceptibility; Endoplasmic Reticulum; Homeostasis; Humans; Lipid Metabolism; Metabolic Networks and Pathways; Neurodegenerative Diseases; Oxidation-Reduction; Peroxisomes; Protein Processing, Post-Translational
PubMed: 32917959
DOI: 10.1038/s12276-020-00503-9