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Sub-cellular Biochemistry 2018A large amount of ultrastructural, biochemical and molecular analysis indicates that peroxisomes and mitochondria not only share the same subcellular space but also... (Review)
Review
A large amount of ultrastructural, biochemical and molecular analysis indicates that peroxisomes and mitochondria not only share the same subcellular space but also maintain considerable overlap in their proteins, responses and functions. Recent approaches using imaging of fluorescent proteins targeted to both organelles in living plant cells are beginning to show the dynamic nature of their interactivity. Based on the observations of living cells, mitochondria respond rapidly to stress by undergoing fission. Mitochondrial fission is suggested to release key membrane-interacting members of the FISSION1 and DYNAMIN RELATED PROTEIN3 families and appears to be followed by the formation of thin peroxisomal extensions called peroxules. In a model we present the peroxules as an intermediate state prior to the formation of tubular peroxisomes, which, in turn are acted upon by the constriction-related proteins released by mitochondria and undergo rapid constriction and fission to increase the number of peroxisomes in a cell. The fluorescent protein aided imaging of peroxisome-mitochondria interaction provides visual evidence for their cooperation in maintenance of cellular homeostasis in plants.
Topics: Mitochondria; Peroxisomes; Plant Cells; Plant Proteins; Plants
PubMed: 30378034
DOI: 10.1007/978-981-13-2233-4_18 -
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 -
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 -
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 -
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 -
Biochimica Et Biophysica Acta May 2016Peroxisomes are dynamic organelles that play an essential role in a variety of cellular catabolic and anabolic metabolic pathways, including fatty acid alpha- and... (Review)
Review
Peroxisomes are dynamic organelles that play an essential role in a variety of cellular catabolic and anabolic metabolic pathways, including fatty acid alpha- and beta-oxidation, and plasmalogen and bile acid synthesis. Defects in genes encoding peroxisomal proteins can result in a large variety of peroxisomal disorders either affecting specific metabolic pathways, i.e., the single peroxisomal enzyme deficiencies, or causing a generalized defect in function and assembly of peroxisomes, i.e., peroxisome biogenesis disorders. In this review, we discuss the clinical, biochemical, and genetic aspects of all human peroxisomal disorders currently known.
Topics: ATPases Associated with Diverse Cellular Activities; Fatty Acids; Gene Expression Regulation; Humans; Membrane Proteins; Metabolic Networks and Pathways; Mutation; Organelle Biogenesis; Oxidation-Reduction; Peroxisomal Disorders; Peroxisomes; Plasmalogens; Protein Isoforms; Protein Sorting Signals; Protein Transport; Signal Transduction
PubMed: 26611709
DOI: 10.1016/j.bbamcr.2015.11.015 -
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 -
Nature Plants Nov 2023Actin-related protein (ARP2/3) complex is a heteroheptameric protein complex, evolutionary conserved in all eukaryotic organisms. Its conserved role is based on the...
Actin-related protein (ARP2/3) complex is a heteroheptameric protein complex, evolutionary conserved in all eukaryotic organisms. Its conserved role is based on the induction of actin polymerization at the interface between membranes and the cytoplasm. Plant ARP2/3 has been reported to participate in actin reorganization at the plasma membrane during polarized growth of trichomes and at the plasma membrane-endoplasmic reticulum contact sites. Here we demonstrate that individual plant subunits of ARP2/3 fused to fluorescent proteins form motile spot-like structures in the cytoplasm that are associated with peroxisomes in Arabidopsis and tobacco. ARP2/3 is found at the peroxisome periphery and contains the assembled ARP2/3 complex and the WAVE/SCAR complex subunit NAP1. This ARP2/3-positive peroxisomal domain colocalizes with the autophagosome and, under conditions that affect the autophagy, colocalization between ARP2/3 and the autophagosome increases. ARP2/3 subunits co-immunoprecipitate with ATG8f and peroxisome-associated ARP2/3 interact in vivo with the ATG8f marker. Since mutants lacking functional ARP2/3 complex have more peroxisomes than wild type, we suggest that ARP2/3 has a novel role in the process of peroxisome degradation by autophagy, called pexophagy.
Topics: Actin-Related Protein 2-3 Complex; Actins; Peroxisomes; Arabidopsis Proteins; Macroautophagy; Arabidopsis
PubMed: 37845336
DOI: 10.1038/s41477-023-01542-6 -
Thrombosis and Haemostasis Mar 2015It is well established that the heart is strongly dependent on fatty acid metabolism. In cardiomyocytes there are two distinct sites for the β-oxidisation of fatty... (Review)
Review
It is well established that the heart is strongly dependent on fatty acid metabolism. In cardiomyocytes there are two distinct sites for the β-oxidisation of fatty acids: the mitochondrion and the peroxisome. Although the metabolism of these two organelles is believed to be tightly coupled, the nature of this relationship has not been fully investigated. Recent research has established the significant contribution of mitochondrial function to cardiac ATP production under normal and pathological conditions. In contrast, limited information is available on peroxisomal function in the heart. This is despite these organelles harbouring metabolic pathways that are potentially cardio-protective, and findings that patients with peroxisomal diseases, such as adult Refsum´s disease, can develop heart failure. In this article, we provide a comprehensive overview on the current knowledge of peroxisomes and the regulation of lipid metabolism by PPARs in cardiomyocytes. We also present new experimental evidence on the differential expression of peroxisome-related genes in the heart chambers and demonstrate that even a mild peroxisomal biogenesis defect (Pex11α-/-) can induce profound alterations in the cardiomyocyte´s peroxisomal compartment and related gene expression, including the concomitant deregulation of specific PPARs. The possible impact of peroxisomal dysfunction in the heart is discussed and a model for the modulation of myocardial metabolism via a peroxisome/PPAR-loop is proposed.
Topics: Animals; Energy Metabolism; Fatty Acids; Gene Expression Regulation; Heart Failure; Humans; Myocytes, Cardiac; Organelle Biogenesis; Peroxisome Proliferator-Activated Receptors; Peroxisomes; Signal Transduction
PubMed: 25608554
DOI: 10.1160/TH14-06-0497