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Sub-cellular Biochemistry 2018As a laboratory animal, Drosophila melanogaster has made extensive contributions to understanding many areas of fundamental biology as well as being an effective model... (Review)
Review
As a laboratory animal, Drosophila melanogaster has made extensive contributions to understanding many areas of fundamental biology as well as being an effective model for human disease. Until recently, there was relatively little known about fly peroxisomes. There were early studies that examined the role of peroxisome enzymes during development of organs like the eye. However, with the advent of a well-annotated, sequenced genome, several groups have collectively determined, first by sequence homology and increasingly by functional studies, Drosophila Peroxins and related peroxisome proteins. Notably, it was shown that Drosophila peroxisome biogenesis is mediated via a well-conserved PTS1 import system. Although the fly genome encodes a Pex7 homologue, a canonical PTS2 import system does not seem to be conserved in Drosophila. Given the homology between Drosophila and Saccharomyces cerevisiae or Homo sapiens peroxisome biogenesis and function, Drosophila has emerged as an effective multicellular system to model human Peroxisome Biogenesis Disorders. Finally, Drosophila peroxisome research has recently come into its own, facilitating new discoveries into the role of peroxisomes within specific tissues, such as testes or immune cells.
Topics: Animals; Disease Models, Animal; Drosophila melanogaster; Humans; Peroxisomal Disorders; Peroxisomes; Saccharomyces cerevisiae
PubMed: 30378026
DOI: 10.1007/978-981-13-2233-4_10 -
Cells Jun 2022The AAA-ATPases Pex1 and Pex6 are required for the formation and maintenance of peroxisomes, membrane-bound organelles that harbor enzymes for specialized metabolism.... (Review)
Review
The AAA-ATPases Pex1 and Pex6 are required for the formation and maintenance of peroxisomes, membrane-bound organelles that harbor enzymes for specialized metabolism. Together, Pex1 and Pex6 form a heterohexameric AAA-ATPase capable of unfolding substrate proteins via processive threading through a central pore. Here, we review the proposed roles for Pex1/Pex6 in peroxisome biogenesis and degradation, discussing how the unfolding of potential substrates contributes to peroxisome homeostasis. We also consider how advances in cryo-EM, computational structure prediction, and mechanisms of related ATPases are improving our understanding of how Pex1/Pex6 converts ATP hydrolysis into mechanical force. Since mutations in and cause the majority of known cases of peroxisome biogenesis disorders such as Zellweger syndrome, insights into Pex1/Pex6 structure and function are important for understanding peroxisomes in human health and disease.
Topics: ATPases Associated with Diverse Cellular Activities; Adenosine Triphosphatases; Homeostasis; Humans; Membrane Proteins; Peroxisomes
PubMed: 35805150
DOI: 10.3390/cells11132067 -
Sub-cellular Biochemistry 2018In a compartmentalized cell, correct protein localization is crucial for function of virtually all cellular processes. From the cytoplasm as a starting point, proteins... (Review)
Review
In a compartmentalized cell, correct protein localization is crucial for function of virtually all cellular processes. From the cytoplasm as a starting point, proteins are imported into organelles by specific targeting signals. Many proteins, however, act in more than one cellular compartment. In this chapter, we discuss mechanisms by which proteins can be targeted to multiple organelles with a focus on a novel gene regulatory mechanism, functional translational readthrough, that permits multiple targeting of proteins to the peroxisome and other organelles. In mammals, lactate and malate dehydrogenase are the best-characterized enzymes whose targeting is controlled by functional translational readthrough.
Topics: Animals; Cytoplasm; Mammals; Peroxisomes; Protein Biosynthesis; Protein Sorting Signals; Protein Transport
PubMed: 30378024
DOI: 10.1007/978-981-13-2233-4_8 -
Methods in Molecular Biology (Clifton,... 2023Computational approaches are practical when investigating putative peroxisomal proteins and for sub-peroxisomal protein localization in unknown protein sequences....
Computational approaches are practical when investigating putative peroxisomal proteins and for sub-peroxisomal protein localization in unknown protein sequences. Nowadays, advancements in computational methods and Machine Learning (ML) can be used to hasten the discovery of novel peroxisomal proteins and can be combined with more established computational methodologies. Here, we explain and list some of the most used tools and methodologies for novel peroxisomal protein detection and localization.
Topics: Peroxisomes; Protein Transport; Amino Acid Sequence; Proteins; Machine Learning
PubMed: 36952202
DOI: 10.1007/978-1-0716-3048-8_29 -
Biochimica Et Biophysica Acta.... Nov 2022Peroxisomes are single-membrane organelles essential for cell metabolism including the β-oxidation of fatty acids, synthesis of etherlipid plasmalogens, and redox... (Review)
Review
Peroxisomes are single-membrane organelles essential for cell metabolism including the β-oxidation of fatty acids, synthesis of etherlipid plasmalogens, and redox homeostasis. Investigations into peroxisome biogenesis and the human peroxisome biogenesis disorders (PBDs) have identified 14 PEX genes encoding peroxins involved in peroxisome biogenesis and the mutation of PEX genes is responsible for the PBDs. Many recent findings have further advanced our understanding of the biology, physiology, and consequences of a functional deficit of peroxisomes. In this Review, we discuss cell defense mechanisms that counteract oxidative stress by 1) a proapoptotic Bcl-2 factor BAK-mediated release to the cytosol of HO-degrading catalase from peroxisomes and 2) peroxisomal import suppression of catalase by Ser232-phosphorylation of Pex14, a docking protein for the Pex5-PTS1 complex. With respect to peroxisome division, the important issue of how the energy-rich GTP is produced and supplied for the division process was recently addressed by the discovery of a nucleoside diphosphate kinase-like protein, termed DYNAMO1 in a lower eukaryote, which has a mammalian homologue NME3. In regard to the mechanisms underlying the pathogenesis of PBDs, a new PBD model mouse defective in Pex14 manifests a dysregulated brain-derived neurotrophic factor (BDNF)-TrkB pathway, an important signaling pathway for cerebellar morphogenesis. Communications between peroxisomes and other organelles are also addressed.
Topics: Animals; Catalase; Homeostasis; Humans; Hydrogen Peroxide; Mammals; Mice; Peroxisomal Disorders; Peroxisomes
PubMed: 35917894
DOI: 10.1016/j.bbamcr.2022.119330 -
Proceedings of the National Academy of... Jan 2020The adaptation of eukaryotic cells to anaerobic conditions is reflected by substantial changes to mitochondrial metabolism and functional reduction. Hydrogenosomes...
The adaptation of eukaryotic cells to anaerobic conditions is reflected by substantial changes to mitochondrial metabolism and functional reduction. Hydrogenosomes belong among the most modified mitochondrial derivative and generate molecular hydrogen concomitant with ATP synthesis. The reduction of mitochondria is frequently associated with loss of peroxisomes, which compartmentalize pathways that generate reactive oxygen species (ROS) and thus protect against cellular damage. The biogenesis and function of peroxisomes are tightly coupled with mitochondria. These organelles share fission machinery components, oxidative metabolism pathways, ROS scavenging activities, and some metabolites. The loss of peroxisomes in eukaryotes with reduced mitochondria is thus not unexpected. Surprisingly, we identified peroxisomes in the anaerobic, hydrogenosome-bearing protist We found a conserved set of peroxin (Pex) proteins that are required for protein import, peroxisomal growth, and division. Key membrane-associated Pexs (Pex3, Pex11, and Pex14) were visualized in numerous vesicles distinct from hydrogenosomes, the endoplasmic reticulum (ER), and Golgi complex. Proteomic analysis of cellular fractions and prediction of peroxisomal targeting signals (PTS1/PTS2) identified 51 putative peroxisomal matrix proteins. Expression of selected proteins in revealed specific targeting to peroxisomes. The matrix proteins identified included components of acyl-CoA and carbohydrate metabolism and pyrimidine and CoA biosynthesis, whereas no components related to either β-oxidation or catalase were present. In conclusion, we identified a subclass of peroxisomes, named "anaerobic" peroxisomes that shift the current paradigm and turn attention to the reductive evolution of peroxisomes in anaerobic organisms.
Topics: Anaerobiosis; Archamoebae; Mitochondria; Oxidation-Reduction; Peroxins; Peroxisomes; Protozoan Proteins; Reactive Oxygen Species
PubMed: 31932444
DOI: 10.1073/pnas.1909755117 -
Biogerontology Oct 2018Peroxisomes are dynamic organelles essential for optimum functioning of a eukaryotic cell. Biogenesis of these organelles and the diverse functions performed by them... (Review)
Review
Peroxisomes are dynamic organelles essential for optimum functioning of a eukaryotic cell. Biogenesis of these organelles and the diverse functions performed by them have been extensively studied in the past decade. Their ability to perform functions depending on the cell type and growth conditions is unique and remarkable. Oxidation of fatty acids and reactive oxygen species metabolism are the two most important functions of these ubiquitous organelles. They are often referred to as both source and sink of reactive oxygen species in a cell. Recent research connects peroxisome dysfunction to fatal oxidative damage associated with ageing-related diseases/disorders. It is now widely accepted that mitochondria and peroxisomes are required to maintain oxidative balance in a cell. However, our understanding on the inter-dependence of these organelles to maintain cellular homeostasis of reactive oxygen species is still in its infancy. Herein, we summarize findings that highlight the role of peroxisomes in cellular reactive oxygen species metabolism, ageing and age-related disorders.
Topics: Aging; Cellular Senescence; Humans; Oxidative Stress; Peroxisomes
PubMed: 29968207
DOI: 10.1007/s10522-018-9761-9 -
The Journal of Eukaryotic Microbiology Nov 2022Kinetoplastea and Diplonemea possess peroxisome-related organelles that, uniquely, contain most of the enzymes of the glycolytic pathway and are hence called glycosomes.... (Review)
Review
Kinetoplastea and Diplonemea possess peroxisome-related organelles that, uniquely, contain most of the enzymes of the glycolytic pathway and are hence called glycosomes. Enzymes of several other core metabolic pathways have also been located in glycosomes, in addition to some characteristic peroxisomal systems such as pathways of lipid metabolism. A considerable amount of research has been performed on glycosomes of trypanosomes since their discovery four decades ago. Not only the role of the glycosomal enzyme systems in the overall cell metabolism appeared to be unique, but also the organelles display remarkable features regarding their biogenesis and structural properties. These features are similar to those of the well-studied peroxisomes of mammalian and plant cells and yeasts yet exhibit also differences reflecting the large evolutionary distance between these protists and the representatives of other major eukaryotic lineages. Despite all research performed, many questions remain about various properties and the biological roles of glycosomes and peroxisomes. Here, we review the current knowledge about glycosomes, often comparing it with information about peroxisomes. Furthermore, we highlight particularly many questions that remain about the biogenesis, and the heterogeneity in structure and content of these enigmatic organelles, and the properties of their boundary membrane.
Topics: Animals; Microbodies; Peroxisomes; Trypanosoma; Euglenozoa; Homeostasis; Mammals
PubMed: 35175680
DOI: 10.1111/jeu.12897 -
FEMS Yeast Research Jun 2016Peroxisomes are ubiquitous organelles found in most eukaryotic cells. In yeasts, peroxisomes play important roles in cell metabolism, especially in different catabolic... (Review)
Review
Peroxisomes are ubiquitous organelles found in most eukaryotic cells. In yeasts, peroxisomes play important roles in cell metabolism, especially in different catabolic processes including fatty acid β-oxidation, the glyoxylic shunt and methanol metabolism, as well as some biosynthetic processes. In addition, peroxisomes are the compartment in which oxidases and catalase are localized. New peroxisomes mainly arise by fission of pre-existing ones, although they can also be formed from the endoplasmic reticulum (ER). Peroxisomes consist of matrix-soluble proteins and membrane proteins known as peroxins. A total of 34 PEX peroxin genes and proteins have been identified to date. and their functions have been elucidated. Protein import into peroxisomes depends on peroxins and requires specific signals in the structure of transported proteins: PTS1, PTS2 and mPTS. The mechanisms of metabolite penetration into peroxisomes are still poorly understood. Peroxisome number and the volume occupied by these organelles are tightly regulated. Methanol, fatty acids and methylamine act as efficient peroxisome proliferators, whereas glucose and ethanol induce peroxisome autophagic degradation (pexophagy). To date, 42 Atg proteins involved in pexophagy are known. Catabolism and alcoholic fermentation of the major pentose sugar, xylose, depend on peroxisomal enzymes. Overexpression of peroxisomal transketolase and transaldolase activates xylose fermentation. Peroxisomes could be useful as target organelles for overexpression of foreign toxic proteins.
Topics: Biotechnology; Industrial Microbiology; Peroxisomes; Saccharomyces cerevisiae
PubMed: 27189367
DOI: 10.1093/femsyr/fow038 -
Trends in Cell Biology Aug 2021Peroxisomes are involved in multiple metabolic processes, including fatty acid oxidation, ether lipid synthesis, and reactive oxygen species (ROS) metabolism. Recent... (Review)
Review
Peroxisomes are involved in multiple metabolic processes, including fatty acid oxidation, ether lipid synthesis, and reactive oxygen species (ROS) metabolism. Recent studies suggest that peroxisomes are critical mediators of cellular responses to various forms of stress, including oxidative stress, hypoxia, starvation, cold exposure, and noise. As dynamic organelles, peroxisomes can modulate their proliferation, morphology, and movement within cells, and engage in crosstalk with other organelles in response to external cues. Although peroxisome-derived hydrogen peroxide has a key role in cellular signaling related to stress, emerging studies suggest that other products of peroxisomal metabolism, such as acetyl-CoA and ether lipids, are also important for metabolic adaptation to stress. Here, we review molecular mechanisms through which peroxisomes regulate metabolic and environmental stress.
Topics: Lipid Metabolism; Oxidation-Reduction; Oxidative Stress; Peroxisomes; Reactive Oxygen Species
PubMed: 33674166
DOI: 10.1016/j.tcb.2021.02.005