-
Cellular and Molecular Life Sciences :... Mar 2021Peroxisomes are organelles that perform a wide range of essential metabolic processes. To ensure that peroxisomes are optimally positioned in the cell, they must be... (Review)
Review
Peroxisomes are organelles that perform a wide range of essential metabolic processes. To ensure that peroxisomes are optimally positioned in the cell, they must be transported by both long- and short-range trafficking events in response to cellular needs. Here, we review our current understanding of the mechanisms by which the cytoskeleton and organelle contact sites alter peroxisomal distribution. Though the focus of the review is peroxisomal transport in mammalian cells, findings from flies and fungi are used for comparison and to inform the gaps in our understanding. Attention is given to the apparent overlap in regulatory mechanisms for mitochondrial and peroxisomal trafficking, along with the recently discovered role of the mitochondrial Rho-GTPases, Miro, in peroxisomal dynamics. Moreover, we outline and discuss the known pathological and pharmacological conditions that perturb peroxisomal positioning. We conclude by highlighting several gaps in our current knowledge and suggest future directions that require attention.
Topics: Animals; Biological Transport; Humans; Microtubules; Mitochondria; Mitochondrial Dynamics; Mitochondrial Proteins; Models, Biological; Peroxisomes; rho GTP-Binding Proteins
PubMed: 33141311
DOI: 10.1007/s00018-020-03687-5 -
Histochemistry and Cell Biology Nov 2018Peroxisomes are key metabolic organelles, which contribute to cellular lipid metabolism, e.g. the β-oxidation of fatty acids and the synthesis of myelin sheath lipids,... (Review)
Review
Peroxisomes are key metabolic organelles, which contribute to cellular lipid metabolism, e.g. the β-oxidation of fatty acids and the synthesis of myelin sheath lipids, as well as cellular redox balance. Peroxisomal dysfunction has been linked to severe metabolic disorders in man, but peroxisomes are now also recognized as protective organelles with a wider significance in human health and potential impact on a large number of globally important human diseases such as neurodegeneration, obesity, cancer, and age-related disorders. Therefore, the interest in peroxisomes and their physiological functions has significantly increased in recent years. In this review, we intend to highlight recent discoveries, advancements and trends in peroxisome research, and present an update as well as a continuation of two former review articles addressing the unsolved mysteries of this astonishing organelle. We summarize novel findings on the biological functions of peroxisomes, their biogenesis, formation, membrane dynamics and division, as well as on peroxisome-organelle contacts and cooperation. Furthermore, novel peroxisomal proteins and machineries at the peroxisomal membrane are discussed. Finally, we address recent findings on the role of peroxisomes in the brain, in neurological disorders, and in the development of cancer.
Topics: Animals; Humans; Organelles; Peroxisomes
PubMed: 30219925
DOI: 10.1007/s00418-018-1722-5 -
Current Opinion in Cell Biology Aug 2015Peroxisomes are remarkably responsive organelles. Their composition, abundance and even their mechanism of biogenesis are influenced strongly by cell type and the... (Review)
Review
Peroxisomes are remarkably responsive organelles. Their composition, abundance and even their mechanism of biogenesis are influenced strongly by cell type and the environment. This plasticity underlies peroxisomal functions in metabolism and the detoxification of dangerous reactive oxygen species. However, peroxisomes are integrated into the cellular system as a whole such that they communicate intimately with other organelles, control signaling dynamics as in the case of innate immune responses to infectious disease, and contribute to processes as fundamental as longevity. The increasing evidence for peroxisomes having roles in various cellular and organismal functions, combined with their malleability, suggests complex mechanisms operate to control cellular dynamics and the specificity of cellular responses and functions extending well beyond the peroxisome itself. A deeper understanding of the functions of peroxisomes and the mechanisms that control their plasticity could offer opportunities for exploiting changes in peroxisome abundance to control cellular function.
Topics: Animals; Humans; Immunity, Innate; Peroxisomes; Reactive Oxygen Species; Signal Transduction; Transcription, Genetic
PubMed: 26042681
DOI: 10.1016/j.ceb.2015.05.002 -
Redox Biology Oct 2023Peroxisomes are metabolically active organelles that are known for exerting oxidative metabolism, but the precise mechanism remains unclear in diabetic nephropathy (DN)....
Peroxisomes are metabolically active organelles that are known for exerting oxidative metabolism, but the precise mechanism remains unclear in diabetic nephropathy (DN). Here, we used proteomics to uncover a correlation between the antioxidant protein disulfide-bond A oxidoreductase-like protein (DsbA-L) and peroxisomal function. In vivo, renal tubular injury, oxidative stress, and cell apoptosis in high-fat diet plus streptozotocin (STZ)-induced diabetic mice were significantly increased, and these changes were accompanied by a "ghost" peroxisomal phenotype, which was further aggravated in DsbA-L-deficient diabetic mice. In vitro, the overexpression of DsbA-L in peroxisomes could improve peroxisomal phenotype and function, reduce oxidative stress and cell apoptosis induced by high glucose (HG, 30 mM) and palmitic acid (PA, 250 μM), but this effect was reversed by 3-Amino-1,2,4-triazole (3-AT, a catalase inhibitor). Mechanistically, DsbA-L regulated the activity of catalase by binding to it, thereby reducing peroxisomal leakage and proteasomal degradation of peroxisomal matrix proteins induced by HG and PA. Additionally, the expression of DsbA-L in renal tubules of patients with DN significantly decreased and was positively correlated with peroxisomal function. Taken together, these results highlight an important role of DsbA-L in ameliorating tubular injury in DN by improving peroxisomal function.
Topics: Animals; Mice; Catalase; Diabetic Nephropathies; Peroxisomes; Diabetes Mellitus, Experimental; Oxidative Stress
PubMed: 37597421
DOI: 10.1016/j.redox.2023.102855 -
Journal of Inherited Metabolic Disease Jan 2020Peroxisomes are multifunctional, dynamic, membrane-bound organelles with important functions in cellular lipid metabolism, rendering them essential for human health and... (Review)
Review
Peroxisomes are multifunctional, dynamic, membrane-bound organelles with important functions in cellular lipid metabolism, rendering them essential for human health and development. Important roles for peroxisomes in signaling and the fine-tuning of cellular processes are emerging, which integrate them in a complex network of interacting cellular compartments. Like many other organelles, peroxisomes communicate through membrane contact sites. For example, peroxisomal growth, positioning, and lipid metabolism involves contacts with the endoplasmic reticulum (ER). Here, we discuss the most recent findings on peroxisome-organelle interactions including peroxisome-ER interplay at membrane contacts sites, and functional interplay with mitochondria, lysosomes, and lipid droplets in mammalian cells. We address tether proteins, metabolic cooperation, and the impact of peroxisome interactions on human health and disease.
Topics: Animals; Disease; Endoplasmic Reticulum; Health; Humans; Lipid Droplets; Lipid Metabolism; Lysosomes; Membrane Proteins; Mitochondria; Mitochondrial Membranes; Organelles; Peroxisomes; Signal Transduction
PubMed: 30864148
DOI: 10.1002/jimd.12083 -
International Journal of Molecular... Sep 2019Peroxisomes are cell organelles that play an important role in plants in many physiological and developmental processes. The plant peroxisomes harbor enzymes of the... (Review)
Review
Peroxisomes are cell organelles that play an important role in plants in many physiological and developmental processes. The plant peroxisomes harbor enzymes of the β-oxidation of fatty acids and the glyoxylate cycle; photorespiration; detoxification of reactive oxygen and nitrogen species; as well as biosynthesis of hormones and signal molecules. The function of peroxisomes in plant cells changes during plant growth and development. They are transformed from organelles involved in storage lipid breakdown during seed germination and seedling growth into leaf peroxisomes involved in photorespiration in green parts of the plant. Additionally, intensive oxidative metabolism of peroxisomes causes damage to their components. Therefore, unnecessary or damaged peroxisomes are degraded by selective autophagy, called pexophagy. This is an important element of the quality control system of peroxisomes in plant cells. Despite the fact that the mechanism of pexophagy has already been described for yeasts and mammals, the molecular mechanisms by which plant cells recognize peroxisomes that will be degraded via pexophagy still remain unclear. It seems that a plant-specific mechanism exists for the selective degradation of peroxisomes. In this review, we describe the physiological role of pexophagy in plant cells and the current hypotheses concerning the mechanism of plant pexophagy.
Topics: Autophagy; Macroautophagy; Microautophagy; Oxidative Stress; Peroxisomes; Plant Physiological Phenomena; Plants; Sugars
PubMed: 31557865
DOI: 10.3390/ijms20194754 -
Biochimica Et Biophysica Acta May 2016This contribution describes the phenotypic differences of yeast peroxisome-deficient mutants (pex mutants). In some cases different phenotypes were reported for yeast... (Review)
Review
This contribution describes the phenotypic differences of yeast peroxisome-deficient mutants (pex mutants). In some cases different phenotypes were reported for yeast mutants deleted in the same PEX gene. These differences are most likely related to the marker proteins and methods used to detect peroxisomal remnants. This is especially evident for pex3 and pex19 mutants, where the localization of receptor docking proteins (Pex13, Pex14) resulted in the identification of peroxisomal membrane remnants, which do not contain other peroxisomal membrane proteins, such as the ring proteins Pex2, Pex10 and Pex12. These structures in pex3 and pex19 cells are the template for peroxisome formation upon introduction of the missing gene. Taken together, these data suggest that in all yeast pex mutants analyzed so far peroxisomes are not formed de novo but use membrane remnant structures as a template for peroxisome formation upon reintroduction of the missing gene. The relevance of this model for peroxisomal membrane protein and lipid sorting to peroxisomes is discussed.
Topics: Animals; Endoplasmic Reticulum; Eukaryotic Cells; 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: 26367802
DOI: 10.1016/j.bbamcr.2015.09.008 -
Trends in Microbiology Nov 2019Peroxisomes are multifunctional organelles with roles in cellular metabolism, cytotoxicity, and signaling. The plastic nature of these organelles allows them to respond... (Review)
Review
Peroxisomes are multifunctional organelles with roles in cellular metabolism, cytotoxicity, and signaling. The plastic nature of these organelles allows them to respond to diverse biological processes, such as virus infections, by remodeling their biogenesis, morphology, and composition to enhance specific functions. During virus infections in humans, peroxisomes act as important immune signaling organelles, aiding the host by orchestrating antiviral signaling. However, more recently it was discovered that peroxisomes can also benefit the virus, facilitating virus-host interactions that rewire peroxisomes to support cellular processes for virus replication and spread. Here, we describe recent studies that uncovered this double-edged character of peroxisomes during infection, highlighting mechanisms that viruses have coevolved to take advantage of peroxisome plasticity. We also provide a perspective for future studies by comparing the established roles of peroxisomes in plant infections and discussing the promise of virology studies as a venue to reveal the uncharted biology of peroxisomes.
Topics: Animals; Biological Evolution; Host Microbial Interactions; Humans; Peroxisomes; Plant Viruses; Viral Tropism; Virus Diseases; Virus Replication
PubMed: 31331665
DOI: 10.1016/j.tim.2019.06.006 -
Cells Sep 2022Although autophagy regulates the quality and quantity of cellular compartments, the regulatory mechanisms underlying peroxisomal autophagy (pexophagy) remain largely...
Although autophagy regulates the quality and quantity of cellular compartments, the regulatory mechanisms underlying peroxisomal autophagy (pexophagy) remain largely unknown. In this study, we identified several BRD4 inhibitors, including molibresib, a novel pexophagy inducer, via chemical library screening. Treatment with molibresib promotes loss of peroxisomes selectively, but not mitochondria, ER, or Golgi apparatus in HeLa cells. Consistently, depletion of BRD4 expression also induced pexophagy in RPE cells. In addition, the inhibition of BRD4 by molibresib increased autophagic degradation of peroxisome ATG7-dependency. We further found that molibresib produced reactive oxygen species (ROS), which potentiates ATM activation. Inhibition of ROS or ATM suppressed the loss of peroxisomes in molibresib-treated cells. Taken together, our data suggest that inhibition of BRD4 promotes pexophagy by increasing ROS and ATM activation.
Topics: Ataxia Telangiectasia Mutated Proteins; Cell Cycle Proteins; HeLa Cells; Humans; Macroautophagy; Nuclear Proteins; Peroxisomes; Reactive Oxygen Species; Transcription Factors
PubMed: 36139416
DOI: 10.3390/cells11182839 -
Nature Communications Aug 2022Membrane contact sites (MCSs) link organelles to coordinate cellular functions across space and time. Although viruses remodel organelles for their replication cycles,...
Membrane contact sites (MCSs) link organelles to coordinate cellular functions across space and time. Although viruses remodel organelles for their replication cycles, MCSs remain largely unexplored during infections. Here, we design a targeted proteomics platform for measuring MCS proteins at all organelles simultaneously and define functional virus-driven MCS alterations by the ancient beta-herpesvirus human cytomegalovirus (HCMV). Integration with super-resolution microscopy and comparisons to herpes simplex virus (HSV-1), Influenza A, and beta-coronavirus HCoV-OC43 infections reveals time-sensitive contact regulation that allows switching anti- to pro-viral organelle functions. We uncover a stabilized mitochondria-ER encapsulation structure (MENC). As HCMV infection progresses, MENCs become the predominant mitochondria-ER contact phenotype and sequentially recruit the tethering partners VAP-B and PTPIP51, supporting virus production. However, premature ER-mitochondria tethering activates STING and interferon response, priming cells against infection. At peroxisomes, ACBD5-mediated ER contacts balance peroxisome proliferation versus membrane expansion, with ACBD5 impacting the titers of each virus tested.
Topics: Cytomegalovirus; Cytomegalovirus Infections; Herpes Simplex; Herpesviridae Infections; Humans; Organelles; Peroxisomes; Viruses
PubMed: 35953480
DOI: 10.1038/s41467-022-32488-6