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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 -
Plant, Cell & Environment Apr 2022Catalase is a well-known component of the cellular antioxidant network, but there have been conflicting conclusions reached regarding the nature of its peroxisome...
Catalase is a well-known component of the cellular antioxidant network, but there have been conflicting conclusions reached regarding the nature of its peroxisome targeting signal. It has also been reported that catalase can be hijacked to the nucleus by effector proteins of plant pathogens. Using a physiologically relevant system where native untagged catalase variants are expressed in a cat2-1 mutant background, the C terminal most 18 amino acids could be deleted without affecting activity, peroxisomal targeting or ability to complement multiple phenotypes of the cat2-1 mutant. In contrast, converting the native C terminal tripeptide PSI to the canonical PTS1 sequence ARL resulted in lower catalase specific activity. Localisation experiments using split superfolder green fluorescent protein revealed that catalase can be targeted to the nucleus in the absence of any pathogen effectors, and that C terminal tagging in combination with alterations of the native C terminus can interfere with nuclear localisation. These findings provide fundamental new insights into catalase targeting and pave the way for exploration of the mechanism of catalase targeting to the nucleus and its role in non-infected plants.
Topics: Catalase; Green Fluorescent Proteins; Peroxisome-Targeting Signal 1 Receptor; Peroxisomes; Receptors, Cytoplasmic and Nuclear
PubMed: 35040158
DOI: 10.1111/pce.14262 -
International Journal of Molecular... Jul 2021Peroxisome abundance is regulated by homeostasis between the peroxisomal biogenesis and degradation processes. Peroxin 16 (PEX16) is a peroxisomal protein involved in...
Peroxisome abundance is regulated by homeostasis between the peroxisomal biogenesis and degradation processes. Peroxin 16 (PEX16) is a peroxisomal protein involved in trafficking membrane proteins for de novo peroxisome biogenesis. The present study demonstrates that PEX16 also modulates peroxisome abundance through pexophagic degradation. PEX16 knockdown in human retinal pigment epithelial-1 cells decreased peroxisome abundance and function, represented by reductions in the expression of peroxisome membrane protein ABCD3 and the levels of cholesterol and plasmalogens, respectively. The activation of pexophagy under PEX16 knockdown was shown by (i) abrogated peroxisome loss under PEX16 knockdown in autophagy-deficient ATG5 knockout cell lines, and (ii) increased autophagy flux and co-localization of p62-an autophagy adaptor protein-with ABCD3 in the presence of the autophagy inhibitor chloroquine. However, the levels of cholesterol and plasmalogens did not recover despite the restoration of peroxisome abundance following chloroquine treatment. Thus, PEX16 is indispensable for maintaining peroxisome homeostasis by regulating not only the commonly known biogenesis pathway but also the autophagic degradation of peroxisomes.
Topics: ATP-Binding Cassette Transporters; Autophagy; Autophagy-Related Protein 5; Cell Line; Gene Knockdown Techniques; Humans; Membrane Proteins; Peroxisomes; Retinal Pigment Epithelium
PubMed: 34360754
DOI: 10.3390/ijms22157989 -
FEBS Letters Mar 2019The peroxisomal membrane protein (PMP) Pex3 and its cytosolic interaction partner Pex19 have been implicated in peroxisomal membrane biogenesis. Although these peroxins... (Review)
Review
The peroxisomal membrane protein (PMP) Pex3 and its cytosolic interaction partner Pex19 have been implicated in peroxisomal membrane biogenesis. Although these peroxins have been extensively studied, no consensus has been reached yet on how they operate. Here, we discuss two major models of their function, namely, in direct insertion of proteins into the peroxisomal membrane or in formation of PMP-containing vesicles from the endoplasmic reticulum (ER). Pex3 can also recruit other proteins to the peroxisomal membrane (e.g., Inp1, Atg30, Atg36), thereby fulfilling roles in other processes such as autophagy and organelle retention. Recent studies indicate that Pex3 and Pex19 can also facilitate sorting of certain membrane proteins to other cellular organelles, including the ER, lipid droplets, and mitochondria.
Topics: Autophagy; Endoplasmic Reticulum; Humans; Intracellular Membranes; Lipoproteins; Membrane Proteins; Models, Biological; Peroxins; Peroxisomes; Protein Binding
PubMed: 30776093
DOI: 10.1002/1873-3468.13340 -
Biochemical Society Transactions Apr 2016Peroxisomes are essential organelles required for proper cell function in all eukaryotic organisms. They participate in a wide range of cellular processes including the... (Review)
Review
Peroxisomes are essential organelles required for proper cell function in all eukaryotic organisms. They participate in a wide range of cellular processes including the metabolism of lipids and generation, as well as detoxification, of hydrogen peroxide (H2O2). Therefore, peroxisome homoeostasis, manifested by the precise and efficient control of peroxisome number and functionality, must be tightly regulated in response to environmental changes. Due to the existence of many physiological disorders and diseases associated with peroxisome homoeostasis imbalance, the dynamics of peroxisomes have been widely examined. The increasing volume of reports demonstrating significant involvement of the autophagy machinery in peroxisome removal leads us to summarize current knowledge of peroxisome degradation in mammalian cells. In this review we present current models of peroxisome degradation. We particularly focus on pexophagy-the selective clearance of peroxisomes through autophagy. We also critically discuss concepts of peroxisome recognition for pexophagy, including signalling and selectivity factors. Finally, we present examples of the pathological effects of pexophagy dysfunction and suggest promising future directions.
Topics: Animals; Autophagy; Humans; Mammals; Models, Biological; Peroxisomes
PubMed: 27068951
DOI: 10.1042/BST20150268 -
International Journal of Molecular... Oct 2019Peroxisomes, which are ubiquitous organelles in all eukaryotes, are highly dynamic organelles that are essential for development and stress responses. Plant peroxisomes... (Review)
Review
Peroxisomes, which are ubiquitous organelles in all eukaryotes, are highly dynamic organelles that are essential for development and stress responses. Plant peroxisomes are involved in major metabolic pathways, such as fatty acid β-oxidation, photorespiration, ureide and polyamine metabolism, in the biosynthesis of jasmonic, indolacetic, and salicylic acid hormones, as well as in signaling molecules such as reactive oxygen and nitrogen species (ROS/RNS). Peroxisomes are involved in the perception of environmental changes, which is a complex process involving the regulation of gene expression and protein functionality by protein post-translational modifications (PTMs). Although there has been a growing interest in individual PTMs in peroxisomes over the last ten years, their role and cross-talk in the whole peroxisomal proteome remain unclear. This review provides up-to-date information on the function and crosstalk of the main peroxisomal PTMs. Analysis of whole peroxisomal proteomes shows that a very large number of peroxisomal proteins are targeted by multiple PTMs, which affect redox balance, photorespiration, the glyoxylate cycle, and lipid metabolism. This multilevel PTM regulation could boost the plasticity of peroxisomes and their capacity to regulate metabolism in response to environmental changes.
Topics: Nitric Oxide; Oxidation-Reduction; Peroxisomes; Plants; Protein Processing, Post-Translational; Proteome; Reactive Oxygen Species; Signal Transduction
PubMed: 31581473
DOI: 10.3390/ijms20194881 -
Biochemical Society Transactions Jun 2010Plant peroxisomes are extremely dynamic, moving and undergoing changes of shape in response to metabolic and environmental signals. Matrix proteins are imported via one... (Review)
Review
Plant peroxisomes are extremely dynamic, moving and undergoing changes of shape in response to metabolic and environmental signals. Matrix proteins are imported via one of two import pathways, depending on the targeting signal within the protein. Each pathway has a specific receptor but utilizes common membrane-bound translocation machinery. Current models invoke receptor recycling, which may involve cycles of ubiquitination. Some components of the import machinery may also play a role in proteolytic turnover of matrix proteins, prompting parallels with the endoplasmic-reticulum-associated degradation pathway. Peroxisome membrane proteins, some of which are imported post-translationally, others of which may traffic to peroxisomes via the endoplasmic reticulum, use distinct proteinaceous machinery. The isolation of mutants defective in peroxisome biogenesis has served to emphasize the important role of peroxisomes at all stages of the plant life cycle.
Topics: Animals; Fatty Acids; Membrane Proteins; Oxidation-Reduction; Peroxisomes; Plant Cells; Plant Proteins; Plants; Signal Transduction
PubMed: 20491668
DOI: 10.1042/BST0380807 -
PloS One 2015We previously found that peroxisomal biogenesis factor 11a (Pex11a) deficiency is associated with a reduction in peroxisome abundance and impaired fatty acid metabolism...
We previously found that peroxisomal biogenesis factor 11a (Pex11a) deficiency is associated with a reduction in peroxisome abundance and impaired fatty acid metabolism in hepatocytes, and results in steatosis. In the present study, we investigated whether butyrate induces Pex11a expression and peroxisome proliferation, and studied its effect on lipid metabolism. C57BL/6 mice fed standard chow or a high-fat diet (HFD) were treated with tributyrin, 4-phelybutyrate acid (4-PBA), or the butyrate-producing probiotics (Clostridium butyricum MIYAIRI 588 [CBM]) plus inulin (dietary fiber), and the body weight, white adipose tissue, serum triglycerides, mRNA expression, and peroxisome abundance were evaluated. Tributyrin or 4-PBA treatment significantly decreased body weight and increased hepatic mRNA expression of peroxisome proliferator-activated receptor-α (PPARα) and Pex11a. In addition, 4-PBA treatment increased peroxisome abundance and the expression of genes involved in peroxisomal fatty acid β-oxidation (acyl-coenzyme A oxidase 1 and hydroxysteroid [17-beta] dehydrogenase 4). CBM and inulin administration reduced adipose tissue mass and serum triglycerides, induced Pex11a, acyl-coenzyme A oxidase 1, and hydroxysteroid (17-beta) dehydrogenase 4 genes, and increased peroxisome abundance in mice fed standard chow or an HFD. In conclusion, elevation of butyrate availability (directly through administration of butyrate or indirectly via administration of butyrate-producing probiotics plus fiber) induces PPARα and Pex11a and the genes involved in peroxisomal fatty acid β-oxidation, increases peroxisome abundance, and improves lipid metabolism. These results may provide a new therapeutic strategy against hyperlipidemia and obesity.
Topics: Animals; Butyrates; Clostridium butyricum; Dietary Supplements; Gene Expression Regulation; Inulin; Male; Membrane Proteins; Mice; PPAR alpha; Peroxisomes; Probiotics
PubMed: 25659146
DOI: 10.1371/journal.pone.0117851 -
Biochimica Et Biophysica Acta Jan 2012Peroxisome is a single-membrane organelle in eukaryotes. The functional importance of peroxisomes in humans is highlighted by peroxisome-deficient peroxisome biogenesis... (Review)
Review
New insights into dynamic and functional assembly of the AAA peroxins, Pex1p and Pex6p, and their membrane receptor Pex26p in shuttling of PTS1-receptor Pex5p during peroxisome biogenesis.
Peroxisome is a single-membrane organelle in eukaryotes. The functional importance of peroxisomes in humans is highlighted by peroxisome-deficient peroxisome biogenesis disorders such as Zellweger syndrome. Two AAA peroxins, Pex1p and Pex6p, are encoded by PEX1 and PEX6, the causal genes for PBDs of complementation groups 1 and 4, respectively. PEX26 responsible for peroxisome biogenesis disorders of complementation group 8 codes for C-tail-anchored type-II membrane peroxin Pex26p, the recruiter of Pex1p-Pex6p complexes to peroxisomes. Pex1p is targeted to peroxisomes in a manner dependent on ATP hydrolysis, while Pex6p targeting requires ATP but not its hydrolysis. Pex1p and Pex6p are most likely regulated in their peroxisomal localization onto Pex26p via conformational changes by ATPase cycle. Pex5p is the cytosolic receptor for peroxisome matrix proteins with peroxisome targeting signal type-1 and shuttles between the cytosol and peroxisomes. AAA peroxins are involved in the export from peroxisomes of Pex5p. Pex5p is ubiquitinated at the conserved cysteine11 in a form associated with peroxisomes. Pex5p with a mutation of the cysteine11 to alanine, termed Pex5p-C11A, abrogates peroxisomal import of proteins harboring peroxisome targeting signals 1 and 2 in wild-type cells. Pex5p-C11A is imported into peroxisomes but not exported, hence suggesting an essential role of the cysteine residue in the export of Pex5p.
Topics: ATPases Associated with Diverse Cellular Activities; Adenosine Triphosphatases; Amino Acid Sequence; Animals; Conserved Sequence; Humans; Membrane Proteins; Peroxisome-Targeting Signal 1 Receptor; Peroxisomes; Protein Multimerization; Protein Structure, Quaternary; Protein Structure, Tertiary; Protein Transport; Receptors, Cytoplasmic and Nuclear
PubMed: 22079764
DOI: 10.1016/j.bbamcr.2011.10.012 -
Current Opinion in Cell Biology Aug 2014Significant progress has been made towards our understanding of the mechanism of peroxisome formation, in particular concerning sorting of peroxisomal membrane proteins,... (Review)
Review
Significant progress has been made towards our understanding of the mechanism of peroxisome formation, in particular concerning sorting of peroxisomal membrane proteins, matrix protein import and organelle multiplication. Here we evaluate the progress made in recent years. We focus mainly on progress made in yeasts. We indicate the gaps in our knowledge and discuss conflicting models.
Topics: Animals; Endoplasmic Reticulum; Humans; Models, Biological; Peroxisomes; Protein Biosynthesis; Protein Transport; Proteins
PubMed: 24681485
DOI: 10.1016/j.ceb.2014.02.002