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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 -
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 -
Biochemical Society Transactions Apr 2023The study of endoplasmic reticulum (ER)-mitochondria communication is a vast and expanding field with many novel developments in the past few years. In this mini-review,... (Review)
Review
The study of endoplasmic reticulum (ER)-mitochondria communication is a vast and expanding field with many novel developments in the past few years. In this mini-review, we focus on several recent publications that identify novel functions of tether complexes, in particular autophagy regulation and lipid droplet biogenesis. We review novel findings that shed light on the role of triple contacts between ER and mitochondria with peroxisomes or lipid droplets as the third player. We also summarize recent findings on the role of ER-mitochondria contacts in human neurodegenerative diseases, which implicate either enhanced or reduced ER-mitochondria contacts in neurodegeneration. Taken together, the discussed studies highlight the need for further research into the role of triple organelle contacts, as well as into the exact mechanisms of increased and decreased ER-mitochondria contacts in neurodegeneration.
Topics: Humans; Mitochondria; Endoplasmic Reticulum; Peroxisomes; Neurodegenerative Diseases; Autophagy
PubMed: 36892405
DOI: 10.1042/BST20221305 -
Cells Jul 2020Peroxisomes are metabolic organelles involved in lipid metabolism and cellular redoxbalance. Peroxisomal function is central to fatty acid oxidation, ether phospholipid... (Review)
Review
Peroxisomes are metabolic organelles involved in lipid metabolism and cellular redoxbalance. Peroxisomal function is central to fatty acid oxidation, ether phospholipid synthesis, bile acidsynthesis, and reactive oxygen species homeostasis. Human disorders caused by genetic mutations inperoxisome genes have led to extensive studies on peroxisome biology. Peroxisomal defects are linkedto metabolic dysregulation in diverse human diseases, such as neurodegeneration and age-relateddisorders, revealing the significance of peroxisome metabolism in human health. Cancer is a diseasewith metabolic aberrations. Despite the critical role of peroxisomes in cell metabolism, the functionaleects of peroxisomes in cancer are not as well recognized as those of other metabolic organelles,such as mitochondria. In addition, the significance of peroxisomes in cancer is less appreciated thanit is in degenerative diseases. In this review, I summarize the metabolic pathways in peroxisomesand the dysregulation of peroxisome metabolism in cancer. In addition, I discuss the potential ofinactivating peroxisomes to target cancer metabolism, which may pave the way for more eectivecancer treatment.
Topics: Animals; Biosynthetic Pathways; Homeostasis; Humans; Models, Biological; Neoplasms; Peroxisomes; Reactive Oxygen Species
PubMed: 32674458
DOI: 10.3390/cells9071692 -
International Journal of Molecular... Jan 2020The removal of damaged or superfluous organelles from the cytosol by selective autophagy is required to maintain organelle function, quality control and overall cellular... (Review)
Review
The removal of damaged or superfluous organelles from the cytosol by selective autophagy is required to maintain organelle function, quality control and overall cellular homeostasis. Precisely how substrate selectivity is achieved, and how individual substrates are degraded during selective autophagy in response to both extracellular and intracellular cues is not well understood. The aim of this review is to highlight pexophagy, the autophagic degradation of peroxisomes, as a model for selective autophagy. Peroxisomes are dynamic organelles whose abundance is rapidly modulated in response to metabolic demands. Peroxisomes are routinely turned over by pexophagy for organelle quality control yet can also be degraded by pexophagy in response to external stimuli such as amino acid starvation or hypoxia. This review discusses the molecular machinery and regulatory mechanisms governing substrate selectivity during both quality-control pexophagy and pexophagy in response to external stimuli, in yeast and mammalian systems. We draw lessons from pexophagy to infer how the cell may coordinate the degradation of individual substrates by selective autophagy across different cellular cues.
Topics: Animals; Autophagy; Macroautophagy; Models, Theoretical; Peroxisomes
PubMed: 31963200
DOI: 10.3390/ijms21020578 -
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 -
Biochemical and Biophysical Research... Jan 2016Pexophagy is the selective degradation of peroxisomes for maintaining peroxisome homeostasis within cells. Peroxisome dynamics and pexophagy are important events...
Pexophagy is the selective degradation of peroxisomes for maintaining peroxisome homeostasis within cells. Peroxisome dynamics and pexophagy are important events required to maintain the quality control of peroxisomes, thereby preventing peroxisome-associated diseases. To identify novel pexophagy modulators, we developed a cell-based screening system and selected 2,2'-dipyridyl (2,2-DP) as a candidate molecule. 2,2-DP treatment induced peroxisome degradation as evidenced by an increased number of low-pH autolysosomes originating from peroxisomes and a decrease in the expression of peroxisomal proteins such as catalase, Pex14, and PMP70. The phenotype was defined as pexophagy, because 2,2-DP induced autophagy and inhibition of autophagy significantly reduced the degree of peroxisome degradation. Mechanistically, 2,2-DP-dependent pexophagy seemed to be mediated by iron chelation, since another iron chelator displayed a similar effect on pexophagy, but a copper chelator did not. Notably, iron replenishment prevented 2,2-DP-mediated pexophagy. Taken together, our results suggest that 2,2-DP treatment disrupts peroxisome dynamics and promotes pexophagy through iron depletion.
Topics: 2,2'-Dipyridyl; Autophagy; Cell Line; Dose-Response Relationship, Drug; Humans; Iron Chelating Agents; Peroxisomes; Retinal Pigment Epithelium
PubMed: 26721431
DOI: 10.1016/j.bbrc.2015.12.098 -
Annual Review of Analytical Chemistry... Jun 2022Cellular organelles are highly specialized compartments with distinct functions. With the increasing resolution of detection methods, it is becoming clearer that same... (Review)
Review
Cellular organelles are highly specialized compartments with distinct functions. With the increasing resolution of detection methods, it is becoming clearer that same organelles may have different functions or properties not only within different cell populations of a tissue but also within the same cell. Dysfunction or altered function affects the organelle itself and may also lead to malignancies or undesirable cell death. To understand cellular function or dysfunction, it is therefore necessary to analyze cellular components at the single-organelle level. Here, we review the recent advances in analyzing cellular function at single-organelle resolution using high-parameter flow cytometry or multicolor confocal microscopy. We focus on the analysis of mitochondria, as they are organelles at the crossroads of various cellular signaling pathways and functions. However, most of the applied methods/technologies are transferable to any other organelle, such as the endoplasmic reticulum, lysosomes, or peroxisomes.
Topics: Endoplasmic Reticulum; Lysosomes; Microscopy, Confocal; Mitochondria; Peroxisomes
PubMed: 35303775
DOI: 10.1146/annurev-anchem-061020-111722 -
Redox Biology Jul 2020Catalase is a powerful antioxidant metalloenzyme located in peroxisomes which also plays a central role in signaling processes under physiological and adverse... (Review)
Review
Catalase is a powerful antioxidant metalloenzyme located in peroxisomes which also plays a central role in signaling processes under physiological and adverse situations. Whereas animals contain a single catalase gene, in plants this enzyme is encoded by a multigene family providing multiple isoenzymes whose number varies depending on the species, and their expression is regulated according to their tissue/organ distribution and the environmental conditions. This enzyme can be modulated by reactive oxygen and nitrogen species (ROS/RNS) as well as by hydrogen sulfide (HS). Catalase is the major protein undergoing Tyr-nitration [post-translational modification (PTM) promoted by RNS] during fruit ripening, but the enzyme from diverse sources is also susceptible to undergo other activity-modifying PTMs. Data on S-nitrosation and persulfidation of catalase from different plant origins are given and compared here with results from obese children where S-nitrosation of catalase occurs. The cysteine residues prone to be S-nitrosated in catalase from plants and from bovine liver have been identified. These evidences assign to peroxisomes a crucial statement in the signaling crossroads among relevant molecules (NO and HS), since catalase is allocated in these organelles. This review depicts a scenario where the regulation of catalase through PTMs, especially S-nitrosation and persulfidation, is highlighted.
Topics: Animals; Catalase; Cattle; Child; Humans; Hydrogen Sulfide; Nitric Oxide; Peroxisomes; Plants; Reactive Nitrogen Species
PubMed: 32505768
DOI: 10.1016/j.redox.2020.101525 -
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