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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 -
Journal of Inherited Metabolic Disease Jul 2015Peroxisomes and mitochondria are ubiquitous, highly dynamic organelles with an oxidative type of metabolism in eukaryotic cells. Over the years, substantial evidence has... (Review)
Review
Peroxisomes and mitochondria are ubiquitous, highly dynamic organelles with an oxidative type of metabolism in eukaryotic cells. Over the years, substantial evidence has been provided that peroxisomes and mitochondria exhibit a close functional interplay which impacts on human health and development. The so-called "peroxisome-mitochondria connection" includes metabolic cooperation in the degradation of fatty acids, a redox-sensitive relationship, an overlap in key components of the membrane fission machineries and cooperation in anti-viral signalling and defence. Furthermore, combined peroxisome-mitochondria disorders with defects in organelle division have been revealed. In this review, we present the latest progress in the emerging field of peroxisomal and mitochondrial interplay in mammals with a particular emphasis on cooperative fatty acid β-oxidation, redox interplay, organelle dynamics, cooperation in anti-viral signalling and the resulting implications for disease.
Topics: Animals; Fatty Acids; Humans; Mitochondria; Mitochondrial Diseases; Mitochondrial Membranes; Oxidation-Reduction; Peroxisomal Disorders; Peroxisomes; Virus Diseases
PubMed: 25687155
DOI: 10.1007/s10545-015-9819-7 -
Sub-cellular Biochemistry 2018Peroxisome proliferation involves signal recognition and computation by molecular networks that direct molecular events of gene expression, metabolism, membrane... (Review)
Review
Peroxisome proliferation involves signal recognition and computation by molecular networks that direct molecular events of gene expression, metabolism, membrane biogenesis, organelle proliferation, protein import, and organelle inheritance. Peroxisome biogenesis in yeast has served as a model system for exploring the regulatory networks controlling this process. Yeast is an outstanding model system to develop tools and approaches to study molecular networks and cellular responses and because the mechanisms of peroxisome biogenesis and key aspects of the transcriptional regulatory networks are remarkably conserved from yeast to humans. In this chapter, we focus on the complex regulatory networks that respond to environmental cues leading to peroxisome assembly and the molecular events of organelle assembly. Ultimately, understanding the mechanisms of the entire peroxisome biogenesis program holds promise for predictive modeling approaches and for guiding rational intervention strategies that could treat human conditions associated with peroxisome function.
Topics: Humans; Metabolic Networks and Pathways; Models, Biological; Peroxisomes; Protein Transport; Saccharomyces cerevisiae
PubMed: 30378032
DOI: 10.1007/978-981-13-2233-4_16 -
Redox Biology 2015Peroxisomes are ubiquitous organelles present in nearly all eukaryotic cells. Conserved functions of peroxisomes encompass beta-oxidation of fatty acids and scavenging... (Review)
Review
Peroxisomes are ubiquitous organelles present in nearly all eukaryotic cells. Conserved functions of peroxisomes encompass beta-oxidation of fatty acids and scavenging of reactive oxygen species generated from diverse peroxisomal metabolic pathways. Peroxisome content, number, and size can change quickly in response to environmental and/or developmental cues. To achieve efficient peroxisome homeostasis, peroxisome biogenesis and degradation must be orchestrated. We review the current knowledge on redox regulated peroxisome biogenesis and degradation with an emphasis on yeasts and plants.
Topics: Catalase; Homeostasis; Humans; Metabolic Networks and Pathways; Oxidation-Reduction; Oxidative Stress; Peroxisomes; Reactive Oxygen Species
PubMed: 25545794
DOI: 10.1016/j.redox.2014.12.006 -
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 -
Sub-cellular Biochemistry 2018The current view on peroxisomes has changed dramatically from being human cell oddities to vital organelles that host several key metabolic pathways. To fulfil over 50... (Review)
Review
The current view on peroxisomes has changed dramatically from being human cell oddities to vital organelles that host several key metabolic pathways. To fulfil over 50 different enzymatic functions, human peroxisomes host either unique peroxisomal proteins or dual-localized proteins. The identification and characterization of the complete peroxisomal proteome in humans is important for diagnosis and treatment of patients with peroxisomal disorders as well as for uncovering novel peroxisomal functions and regulatory modules. Hence, here we compiled a comprehensive list of mammalian peroxisomal and peroxisome-associated proteins by curating results of several quantitative and non-quantitative proteomic studies together with entries in the UniProtKB and Compartments knowledge channel databases. Our analysis gives a holistic view on the mammalian peroxisomal proteome and brings to light potential new peroxisomal and peroxisome-associated proteins. We believe that this dataset, represents a valuable surrogate map of the human peroxisomal proteome.
Topics: Animals; Humans; Metabolic Networks and Pathways; Peroxisomal Disorders; Peroxisomes; Proteome; Proteomics
PubMed: 30378018
DOI: 10.1007/978-981-13-2233-4_2 -
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 -
Proceedings of the Japan Academy.... 2016Peroxisome is a single-membrane-bounded ubiquitous organelle containing a hundred different enzymes that catalyze various metabolic pathways such as β-oxidation of very... (Review)
Review
Peroxisome is a single-membrane-bounded ubiquitous organelle containing a hundred different enzymes that catalyze various metabolic pathways such as β-oxidation of very long-chain fatty acids and synthesis of plasmalogens. To investigate peroxisome biogenesis and human peroxisome biogenesis disorders (PBDs) including Zellweger syndrome, more than a dozen different complementation groups of Chinese hamster ovary (CHO) cell mutants impaired in peroxisome biogenesis are isolated as a model experimental system. By taking advantage of rapid functional complementation assay of the CHO cell mutants, successful cloning of PEX genes encoding peroxins required for peroxisome assembly invaluably contributed to the accomplishment of cloning of pathogenic genes responsible for PBDs. Peroxins are divided into three groups: 1) peroxins including Pex3p, Pex16p and Pex19p, are responsible for peroxisome membrane biogenesis via Pex19p- and Pex3p-dependent class I and Pex19p- and Pex16p-dependent class II pathways; 2) peroxins that function in matrix protein import; 3) those such as Pex11pβ are involved in peroxisome division where DLP1, Mff, and Fis1 coordinately function.
Topics: Animals; CHO Cells; Cricetinae; Cricetulus; Humans; Peroxisomal Disorders; Peroxisomes
PubMed: 27941306
DOI: 10.2183/pjab.92.463 -
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 -
Archives of Pharmacal Research May 2019Peroxisomes and their (patho-)physiological importance in heath and disease have attracted increasing interest during last few decades. Together with mitochondria,... (Review)
Review
Peroxisomes and their (patho-)physiological importance in heath and disease have attracted increasing interest during last few decades. Together with mitochondria, peroxisomes comprise key metabolic platforms for oxidation of various fatty acids and redox regulation. In addition, peroxisomes contribute to bile acid, cholesterol, and plasmalogen biosynthesis. The importance of functional peroxisomes for cellular metabolism is demonstrated by the marked brain and systemic organ abnormalities occuring in peroxisome biogenesis disorders and peroxisomal enzyme deficiencies. Current evidences indicate that peroxisomal function is declined with aging, with peroxisomal dysfunction being linked to early onset of multiple age-related diseases including neurodegenerative diseases. Herein, we review recent progress toward understanding the physiological roles and pathological implications of peroxisomal dysfunctions, focusing on neurodegenerative disease.
Topics: Aging; Animals; Brain; Disease Models, Animal; Humans; Lipid Metabolism; Neurodegenerative Diseases; Oxidation-Reduction; Peroxisomal Disorders; Peroxisomes; Reactive Oxygen Species
PubMed: 30739266
DOI: 10.1007/s12272-019-01131-2