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Journal of Cell Science Aug 2023Peroxisomes are involved in a multitude of metabolic and catabolic pathways, as well as the innate immune system. Their dysfunction is linked to severe... (Review)
Review
Peroxisomes are involved in a multitude of metabolic and catabolic pathways, as well as the innate immune system. Their dysfunction is linked to severe peroxisome-specific diseases, as well as cancer and neurodegenerative diseases. To ensure the ability of peroxisomes to fulfill their many roles in the organism, more than 100 different proteins are post-translationally imported into the peroxisomal membrane and matrix, and their functionality must be closely monitored. In this Review, we briefly discuss the import of peroxisomal membrane proteins, and we emphasize an updated view of both classical and alternative peroxisomal matrix protein import pathways. We highlight different quality control pathways that ensure the degradation of dysfunctional peroxisomal proteins. Finally, we compare peroxisomal matrix protein import with other systems that transport folded proteins across membranes, in particular the twin-arginine translocation (Tat) system and the nuclear pore.
Topics: Membrane Proteins; Peroxisomes; Protein Transport; Intracellular Membranes
PubMed: 37552037
DOI: 10.1242/jcs.260999 -
Journal of Visualized Experiments : JoVE May 2023Mammalian cells can turn over peroxisomes through Stub1-mediated pexophagy. The pathway potentially permits cellular control of the quantity and quality of peroxisomes....
Mammalian cells can turn over peroxisomes through Stub1-mediated pexophagy. The pathway potentially permits cellular control of the quantity and quality of peroxisomes. During this process, heat shock protein 70 and the ubiquitin E3 ligase, Stub1, translocate onto peroxisomes to be turned over to initiate pexophagy. The Stub1 ligase activity allows the accumulation of ubiquitin and other autophagy-related modules on targeted peroxisomes. Elevating reactive oxygen species (ROS) levels within the peroxisomal lumen can activate Stub1-mediated pexophagy. One can, therefore, use dye-assisted ROS generation to trigger and monitor this pathway. This article outlines the procedures for using two classes of dyes, fluorescent proteins and synthetic fluorophores, to initiate pexophagy within mammalian cell cultures. These dye-assisted ROS generation-based protocols can not only be used to target all the peroxisomes within a cell population globally but can also permit the manipulation of individual peroxisomes within single cells. We also describe how Stub1-mediated pexophagy can be followed using live-cell microscopy.
Topics: Animals; Macroautophagy; Reactive Oxygen Species; Autophagy; Proteins; Ubiquitin; Mammals; Peroxisomes
PubMed: 37246878
DOI: 10.3791/65010 -
Sub-cellular Biochemistry 2018Peroxisomes in fungi are involved in a huge number of different metabolic processes. In addition, non-metabolic functions have also been identified. The proteins that... (Review)
Review
Peroxisomes in fungi are involved in a huge number of different metabolic processes. In addition, non-metabolic functions have also been identified. The proteins that are present in a particular peroxisome determine its metabolic function, whether they are the matrix localized enzymes of the different metabolic pathways or the membrane proteins involved in transport of metabolites across the peroxisomal membrane. Other peroxisomal proteins play a role in organelle biogenesis and dynamics, such as fission, transport and inheritance. Hence, obtaining a complete overview of which proteins are present in peroxisomes at a given time or under a given growth condition provides invaluable insights into peroxisome biology. Bottom up approaches are ideal to follow one or a few proteins at a time but they are not able to give a global view of the content of peroxisomes. To gain such information, top down approaches are required and one that has provided valuable insights into peroxisome function is mass spectrometry based organellar proteomics. Here, we discuss the findings of several such studies in yeast and filamentous fungi and outline new insights into peroxisomal function that were gained from these studies.
Topics: Fungi; Peroxisomes; Proteomics; Yeasts
PubMed: 30378019
DOI: 10.1007/978-981-13-2233-4_3 -
Biochemical Society Transactions Feb 2021Kinetoplastid parasites have essential organelles called glycosomes that are analogous to peroxisomes present in other eukaryotes. While many of the processes that... (Review)
Review
Kinetoplastid parasites have essential organelles called glycosomes that are analogous to peroxisomes present in other eukaryotes. While many of the processes that regulate glycosomes are conserved, there are several unique aspects of their biology that are divergent from other systems and may be leveraged as therapeutic targets for the treatment of kinetoplastid diseases. Glycosomes are heterogeneous organelles that likely exist as sub-populations with different protein composition and function in a given cell, between individual cells, and between species. However, the limitations posed by the small size of these organelles makes the study of this heterogeneity difficult. Recent advances in the analysis of small vesicles by flow-cytometry provide an opportunity to overcome these limitations. In this review, we describe studies that document the diverse nature of glycosomes and propose an approach to using flow cytometry and organelle sorting to study the diverse composition and function of these organelles. Because the cellular machinery that regulates glycosome protein import and biogenesis is likely to contribute, at least in part, to glycosome heterogeneity we highlight some ways in which the glycosome protein import machinery differs from that of peroxisomes in other eukaryotes.
Topics: Animals; Kinetoplastida; Microbodies; Peroxisomes; Protein Transport; Protozoan Proteins
PubMed: 33439256
DOI: 10.1042/BST20190517 -
Journal of Integrative Plant Biology Feb 2023Protein ubiquitination regulates diverse cellular processes in eukaryotic organisms, from growth and development to stress response. Proteins subjected to ubiquitination... (Review)
Review
Protein ubiquitination regulates diverse cellular processes in eukaryotic organisms, from growth and development to stress response. Proteins subjected to ubiquitination can be found in virtually all subcellular locations and organelles, including peroxisomes, single-membrane and highly dynamic organelles ubiquitous in eukaryotes. Peroxisomes contain metabolic functions essential to plants and animals such as lipid catabolism, detoxification of reactive oxygen species (ROS), biosynthesis of vital hormones and cofactors, and photorespiration. Plant peroxisomes possess a complex proteome with functions varying among different tissue types and developmental stages, and during plant response to distinct environmental cues. However, how these diverse functions are regulated at the post-translational level is poorly understood, especially in plants. In this review, we summarized current knowledge of the involvement of protein ubiquitination in peroxisome protein import, remodeling, pexophagy, and metabolism, focusing on plants, and referencing discoveries from other eukaryotic systems when relevant. Based on previous ubiquitinomics studies, we compiled a list of 56 ubiquitinated Arabidopsis peroxisomal proteins whose functions are associated with all the major plant peroxisomal metabolic pathways. This discovery suggests a broad impact of protein ubiquitination on plant peroxisome functions, therefore substantiating the need to investigate this significant regulatory mechanism in peroxisomes at more depths.
Topics: Animals; Peroxisomes; Ubiquitination; Plants; Arabidopsis; Arabidopsis Proteins
PubMed: 35975710
DOI: 10.1111/jipb.13346 -
The Journal of Biological Chemistry Jul 2022An ever-increasing number of proteins have been shown to translocate across various membranes of bacterial as well as eukaryotic cells in their folded states as a part... (Review)
Review
An ever-increasing number of proteins have been shown to translocate across various membranes of bacterial as well as eukaryotic cells in their folded states as a part of physiological and/or pathophysiological processes. Herein, we provide an overview of the systems/processes that are established or likely to involve the membrane translocation of folded proteins, such as protein export by the twin-arginine translocation system in bacteria and chloroplasts, unconventional protein secretion and protein import into the peroxisome in eukaryotes, and the cytosolic entry of proteins (e.g., bacterial toxins) and viruses into eukaryotes. We also discuss the various mechanistic models that have previously been proposed for the membrane translocation of folded proteins including pore/channel formation, local membrane disruption, membrane thinning, and transport by membrane vesicles. Finally, we introduce a newly discovered vesicular transport mechanism, vesicle budding and collapse, and present evidence that vesicle budding and collapse may represent a unifying mechanism that drives some (and potentially all) of folded protein translocation processes.
Topics: Bacteria; Bacterial Proteins; Eukaryota; Membrane Transport Proteins; Peroxisomes; Protein Folding; Protein Sorting Signals; Protein Transport; Twin-Arginine-Translocation System
PubMed: 35671825
DOI: 10.1016/j.jbc.2022.102107 -
Journal of Cellular and Molecular... Jun 2022The generation of vesicles is a constitutive attribute of mitochondria inherited from bacterial ancestors. The physiological conditions and mild oxidative stress promote... (Review)
Review
The generation of vesicles is a constitutive attribute of mitochondria inherited from bacterial ancestors. The physiological conditions and mild oxidative stress promote oxidation and dysfunction of certain proteins and lipids within the mitochondrial membranes; these constituents are subsequently packed as small mitochondrial-derived vesicles (MDVs) (70-150 nm in diameter) and are transported intracellularly to lysosomes and peroxisomes to be degraded. In this way, MDVs remove the damaged mitochondrial components, preserve mitochondrial structural and functional integrity and restore homeostasis. An outline of the current knowledge on MDVs seems to be necessary for understanding the potential impact of this research area in cellular (patho)physiology. The present synopsis is an attempt towards the accomplishment of this demand, highlighting also the still unclear issues related to MDVs. Here, we discuss (i) MDVs budding and generation (molecules and mechanisms), (ii) the distinct cargoes packed and transported by MDVs, (iii) the MDVs trafficking pathways and (iv) the biological role of MDVs, from quality controllers to the involvement in organellar crosstalk, mitochondrial antigen presentation and peroxisome de novo biogenesis. These complex roles uncover also mitochondria integration into the cellular environment. As the therapeutic exploitation of MDVs is currently limited, future insights into MDVs cell biology are expected to direct to novel diagnostic tools and treatments.
Topics: Biological Transport; Lysosomes; Mitochondria; Oxidation-Reduction; Peroxisomes; Ubiquitin-Protein Ligases
PubMed: 35582908
DOI: 10.1111/jcmm.17391 -
Sub-cellular Biochemistry 2018Plant peroxisomes are required for a number of fundamental physiological processes, such as primary and secondary metabolism, development and stress response. Indexing... (Review)
Review
Plant peroxisomes are required for a number of fundamental physiological processes, such as primary and secondary metabolism, development and stress response. Indexing the dynamic peroxisome proteome is prerequisite to fully understanding the importance of these organelles. Mass Spectrometry (MS)-based proteome analysis has allowed the identification of novel peroxisomal proteins and pathways in a relatively high-throughput fashion and significantly expanded the list of proteins and biochemical reactions in plant peroxisomes. In this chapter, we summarize the experimental proteomic studies performed in plants, compile a list of ~200 confirmed Arabidopsis peroxisomal proteins, and discuss the diverse plant peroxisome functions with an emphasis on the role of Arabidopsis MS-based proteomics in discovering new peroxisome functions. Many plant peroxisome proteins and biochemical pathways are specific to plants, substantiating the complexity, plasticity and uniqueness of plant peroxisomes. Mapping the full plant peroxisome proteome will provide a knowledge base for the improvement of crop production, quality and stress tolerance.
Topics: Arabidopsis; Arabidopsis Proteins; Peroxisomes; Plant Cells; Proteome; Proteomics
PubMed: 30378017
DOI: 10.1007/978-981-13-2233-4_1 -
International Journal of Molecular... May 2017Over the past decades, peroxisomes have emerged as key regulators in overall cellular lipid and reactive oxygen species metabolism. In mammals, these organelles have... (Review)
Review
Over the past decades, peroxisomes have emerged as key regulators in overall cellular lipid and reactive oxygen species metabolism. In mammals, these organelles have also been recognized as important hubs in redox-, lipid-, inflammatory-, and innate immune-signaling networks. To exert these activities, peroxisomes must interact both functionally and physically with other cell organelles. This review provides a comprehensive look of what is currently known about the interconnectivity between peroxisomes and mitochondria within mammalian cells. We first outline how peroxisomal and mitochondrial abundance are controlled by common sets of - and -acting factors. Next, we discuss how peroxisomes and mitochondria may communicate with each other at the molecular level. In addition, we reflect on how these organelles cooperate in various metabolic and signaling pathways. Finally, we address why peroxisomes and mitochondria have to maintain a healthy relationship and why defects in one organelle may cause dysfunction in the other. Gaining a better insight into these issues is pivotal to understanding how these organelles function in their environment, both in health and disease.
Topics: Animals; Cellular Senescence; Fatty Acids; Humans; Metabolic Networks and Pathways; Mitochondria; Oxidation-Reduction; Peroxisomes; Reactive Oxygen Species; Signal Transduction
PubMed: 28538669
DOI: 10.3390/ijms18061126 -
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