Kyushu University Academic Staff Educational and Research Activities Database
List of Books
Masanori Honsho Last modified date:2022.05.18

Associate Professor / Department of Neuroinflammation and Brain Fatigue Science / Faculty of Medical Sciences


Books
1. Okumoto K., Tamura S., Honsho M., and Fujiki Y., Peroxisome: Metabolic Functions and Biogenesis, Springer, Cham, 10.1007/978-3-030-60204-8_1, Lizard G. (eds) Peroxisome Biology: Experimental Models, Peroxisomal Disorders and Neurological Diseases. Advances in Experimental Medicine and Biology, vol 1299, 3-17, 2021.01, Peroxisome is an organelle conserved in almost all eukaryotic cells with a variety of functions in cellular metabolism, including fatty acid β-oxidation, synthesis of ether glycerolipid plasmalogens, and redox homeostasis. Such metabolic functions and the exclusive importance of peroxisomes have been highlighted in fatal human genetic disease called peroxisomal biogenesis disorders (PBDs). Recent advances in this field have identified over 30 PEX genes encoding peroxins as essential factors for peroxisome biogenesis in various species from yeast to humans. Functional delineation of the peroxins has revealed that peroxisome biogenesis comprises the processes, involving peroxisomal membrane assembly, matrix protein import, division, and proliferation. Catalase, the most abundant peroxisomal enzyme, catalyzes decomposition of hydrogen peroxide. Peroxisome plays pivotal roles in the cellular redox homeostasis and the response to oxidative stresses, depending on intracellular localization of catalase..
2. Abe Y., Tamura S., Honsho M., and Fujiki Y., A Mouse Model System to Study Peroxisomal Roles in Neurodegeneration of Peroxisome Biogenesis Disorders, Springer, Cham, 10.1007/978-3-030-60204-8_10, Lizard G. (eds) Peroxisome Biology: Experimental Models, Peroxisomal Disorders and Neurological Diseases. Advances in Experimental Medicine and Biology, vol 1299, 119-143, 2021.01, Fourteen PEX genes are currently identified as genes responsible for peroxisome biogenesis disorders (PBDs). Patients with PBDs manifest as neurodegenerative symptoms such as neuronal migration defect and malformation of the cerebellum. To address molecular mechanisms underlying the pathogenesis of PBDs, mouse models for the PBDs have been generated by targeted disruption of Pex genes. Pathological phenotypes and metabolic abnormalities in Pex-knockout mice well resemble those of the patients with PBDs. The mice with tissue- or cell type-specific inactivation of Pex genes have also been established by using a Cre-loxP system. The genetically modified mice reveal that pathological phenotypes of PBDs are mediated by interorgan and intercellular communications. Despite the illustrations of detailed pathological phenotypes in the mutant mice, mechanistic insights into pathogenesis of PBDs are still underway. In this chapter, we overview the phenotypes of Pex-inactivated mice and the current understanding of the pathogenesis underlying PBDs..
3. Honsho M., Okumoto K., Tamura S., and Fujiki Y., Peroxisome Biogenesis Disorders, Springer, Cham, 10.1007/978-3-030-60204-8_4, Lizard G. (eds) Peroxisome Biology: Experimental Models, Peroxisomal Disorders and Neurological Diseases. Advances in Experimental Medicine and Biology, vol 1299, 45-54, 2021.01, Peroxisomes are presented in all eukaryotic cells and play essential roles in many of lipid metabolic pathways, including β-oxidation of fatty acids and synthesis of ether-linked glycerophospholipids, such as plasmalogens. Impaired peroxisome biogenesis, including defects of membrane assembly, import of peroxisomal matrix proteins, and division of peroxisome, causes peroxisome biogenesis disorders (PBDs). Fourteen complementation groups of PBDs are found, and their complementing genes termed PEXs are isolated. Several new mutations in peroxins from patients with mild PBD phenotype or patients with phenotypes unrelated to the commonly observed impairments of PBD patients are found by next-generation sequencing. Exploring a dysfunctional step(s) caused by the mutation is important for unveiling the pathogenesis of novel mutation by means of cellular and biochemical analyses..
4. Honsho M. and Fujiki Y., Homeostasis of Plasmalogens in Mammals, Elsevier Inc., 10.1016/B978-0-08-100596-5.21664-8, Encyclopedia of Food Chemistry, Elsevier Inc., Waltham, USA. Vol. 2, 218-223, 2019.01, Ethanolamine-containing alkenyl ether glycerophospholipid, plasmalogen, is characterized by the presence of vinyl-ether linkage at the sn-1 position. Plasmalogens are found in nearly all mammalian tissues, and important components of cellular membranes. De novo synthesis of plasmalogens initiated in peroxisomes plays a pivotal role in the homeostasis of cellular plasmalogens. Synthesis of plasmalogens is regulated by feedback mechanism via sensing the plasmalogens located in the inner leaflet of plasma membranes, followed by modulating the level of fatty acyl-CoA reductase 1, the enzyme responsible for the synthesis of long-chain alcohols which are essential for the ether-bond formation in peroxisomes. Plasmalogens can be synthesized from alkylglycerol in cells and peripheral tissues such as liver and heart in rodent, whereas plasmalogens essential for the function of brain are more likely supplied by de novo synthesis in brain rather than the transport of peripherally synthesized plasmalogens by crossing blood brain barrier, implying that regulation of plasmalogen synthesis plays an important role in the homeostasis of brain plasmalogens..
5. Honsho M., and Fujiki Y., Analysis of Plasmalogen Synthesis in Cultured Cells, Humana, 10.1007/978-1-4939-6937-1_6, Schrader, M. (ed.) Peroxisomes: Methods and Protocols, Methods in Molecular Biology 55-61, 2017.01, Plasmalogen synthesis can be analyzed by metabolic labeling, followed by the separation of ethanolamine plasmalogens from glycerophospholipids on one-dimensional thin-layer chromatography. The vinyl-ether bond of plasmalogens is acid-labile, which allows separating plasmalogens as 2-acyl-glycerophospholipids from diacyl-glycerophospholipids..
6. Liu Y., Honsho M., and Fujiki Y., In Vitro PMP Import Analysis Using Cell-Free Synthesized PMP and Isolated Peroxisomes, Humana, 10.1007/978-1-4939-6937-1_19, Schrader, M. (ed.) Peroxisomes: Methods and Protocols, Methods in Molecular Biology 207-212, 2017.01, The Pex19p- and Pex3p-dependent direct import of peroxisomal membrane proteins (PMPs), termed the class I pathway, can be reconstituted in vitro by incubating cell-free synthesized PMPs with highly purified peroxisomes at 26 °C for 1 h. This method ensures that the proteins targeted to peroxisomes are imported directly without involvement of other organelles..
7. Okumoto K., Honsho M., Liu Y., and Fujiki Y., Peroxisomal Membrane and Matrix Protein Import Using a Semi-Intact Mammalian Cell System, Humana, 10.1007/978-1-4939-6937-1_20, Schrader, M. (ed.) Peroxisomes: Methods and Protocols, Methods in Molecular Biology 213-219, 2017.01, Peroxisomes are essential intracellular organelles that catalyze a number of essential metabolic pathways including β-oxidation of very long chain fatty acids, synthesis of plasmalogen, bile acids, and generation and degradation of hydrogen peroxide. These peroxisomal functions are accomplished by strictly and spatiotemporally regulated compartmentalization of the enzymes catalyzing these reactions. Defects in peroxisomal protein import result in inherited peroxisome biogenesis disorders in humans. Peroxisomal matrix and membrane proteins are synthesized on free ribosomes and transported to peroxisomes in a manner dependent on their specific targeting signals and their receptors. Peroxisomal protein import can be analyzed using a semi-intact assay system, in which targeting efficiency is readily monitored by immunofluorescence microscopy. Furthermore, cytosolic factors required for peroxisomal protein import can be manipulated, suggesting that the semi-intact system is a useful and convenient system to uncover the molecular mechanisms of peroxisomal protein import..
8. Fujiki Y., Okumoto K., and Honsho M., Protein Import into Peroxisomes: The Principles and Methods of Studying (version 2.0), John Wiley & Sons, 10.1002/9780470015902.a0002618.pub2, Encyclopedia of Life Sciences, 2015.04, Peroxisomes are essential intracellular organelles that involve many metabolic processes, such as β‐oxidation of very long‐chain fatty acids and synthesis of plasmalogen and bile acids as well as generation and degradation of hydrogen peroxide. These peroxisomal functions are fulfilled by strictly and spatiotemporally regulated compartmentation of the proteins catalysing these reactions. Defects in peroxisomal protein import results in inherited peroxisome biogenesis disorders in humans. Peroxisomal matrix and membrane proteins are synthesised on free ribosomes but transported into peroxisomes by distinct pathways determined by specific targeting signals and their receptors. The mechanism by which this is achieved has been clarified by identification of many PEX genes and the products named peroxins, the essential factors for peroxisome biogenesis. This article introduces several basic methods to investigate protein import into peroxisomes..
9. Fujiki Y., Itoyama A., Abe Y., and Honsho M., Molecular Complex Coordinating Peroxisome Morphogenesis in Mammalian Cells , Springer-Verlag Wien, 10.1007/978-3-7091-1788-0_17, Brocard, C. and Hartig, A. (eds) Molecular machines involved in peroxisome biogenesis and maintenance, Springer-Verlag, Wien, Austria. 391-401, 2014.05, Peroxisomal division comprises three stages: elongation, constriction, and fission. Potential candidates thus far studied for the factors involved in these stages include Pex11pβ, dynamin-like protein 1 (DLP1), mitochondrial fission factor (Mff), and Fission 1 (Fis1). A poly-unsaturated fatty acid of peroxisomal β-oxidation metabolites, docosahexaenoic acid (C22:6n-3), augments hyper-oligomerization of Pex11pβ that gives rise to peroxisomal elongation, a prerequisite for subsequent fission and peroxisome division. Translocation of DLP1, a member of the large GTPase family, from the cytosol to peroxisomes is a prerequisite for membrane fission. However, the molecular machinery for peroxisomal targeting of DLP1 remains elusive. Mff is also localized to peroxisomes, especially at the membrane-constricted regions of elongated peroxisomes. Knockdown of Mff abrogates the fission stage of peroxisomal division and fails to recruit DLP1 to peroxisomes, while ectopic expression of Mff increases the peroxisomal targeting of DLP1. Co-expression of Mff and Pex11pβ increases peroxisome abundance. Overexpression of Mff also increases the interaction between DLP1 and Pex11pβ, which knockdown of Mff, but not Fis1, abolishes. Moreover, Pex11pβ interacts with Mff in a DLP1-dependent manner. Mff contributes to the peroxisomal targeting of DLP1 and plays a key role in the fission of the peroxisomal membrane by acting in concert with Pex11pβ and DLP1. The investigations performed to date suggest that a functional complex comprising Pex11pβ, Mff, and DLP1 promotes Mff-mediated fission during peroxisomal division. With regard to peroxisome morphogenesis, we address recent issues and findings and propose a model for peroxisome division..
10. Schuck S., Honsho M., and Simons K., Detergent-Resistant Membranes and the Use of Cholesterol Depletion, Elsevier Inc., 10.1016/B978-012164730-8/50073-3, Cell Biology : A Laboratory Handbook 2, 5-9, 2006.12.