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https://www.readbyqxmd.com/read/28409469/experimental-systems-to-study-yeast-pexophagy
#1
Shun-Ichi Yamashita, Masahide Oku, Yasuyoshi Sakai, Yukio Fujiki
Peroxisome abundance is tightly regulated according to the physiological contexts, through regulations of both proliferation and degradation of the organelles. Here, we describe detailed methods to analyze processes for autophagic degradation of peroxisomes, termed pexophagy, in yeast organisms. The assay systems include a method for biochemical detection of pexophagy completion, and one for microscopic visualization of specialized membrane structures acting in pexophagy. As a model yeast organism utilized in studies of pexophagy, the methylotrophic yeast Komagataella phaffii (Pichia pastoris) is referred to in this chapter and related information on the studies with baker's yeast (Saccharomyces cerevisiae) is also included...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28409468/assessing-pexophagy-in-mammalian-cells
#2
Shun-Ichi Yamashita, Yukio Fujiki
In mammalian cells several hundred peroxisomes are maintained by a balance between the biogenesis and turnover by peroxisome homeostasis. Pexophagy, a form of autophagy specific for peroxisomes, is the main pathway for peroxisome degradation, but molecular mechanisms of mammalian pexophagy are largely unknown. This is due to the lack of well-established pexophagy-inducing conditions in mammalian cells. Recently, several conditions that induce pexophagy were described for mammalian cells, involving ubiquitin and adaptor proteins of autophagy...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28318378/pexophagy-is-responsible-for-65-of-cases-of-peroxisome-biogenesis-disorders
#3
Taras Y Nazarko
Peroxisome biogenesis disorders (PBDs) is a group of diseases caused by mutations in one of the peroxins, proteins responsible for biogenesis of the peroxisomes. In recent years, it became clear that many peroxins (e.g., PEX3 and PEX14) play additional roles in peroxisome homeostasis (such as promoting autophagic degradation of peroxisomes or pexophagy), which are often opposite to their originally established functions in peroxisome formation and maintenance. Even more interesting, the peroxins that make up the peroxisomal AAA ATPase complex (AAA-complex) in yeast (Pex1, Pex6 and Pex15) or mammals (PEX1, PEX6, PEX26) are responsible for the downregulation of pexophagy...
February 28, 2017: Autophagy
https://www.readbyqxmd.com/read/28255846/peroxisomes-proliferation-and-pharmacological-stimulation-of-autophagy-in-rat-liver-evidence-to-support-that-autophagy-may-remove-the-older-peroxisomes
#4
Gabriella Cavallini, Alessio Donati, Michele Taddei, Ettore Bergamini
Like mitochondria, peroxisomes produce reactive oxygen species (ROS), compounds which have been implicated to play an important role in many degenerative diseases and aging itself, and an exaggerated ROS production might occur in altered or older organelles. Growing evidence shows that autophagy, a required function in cell housekeeping during fasting, can remove damaged macromolecules, organelles, and membranes selectively. Proliferation of peroxisomes can be enhanced in liver cells by perfluorooctanoic acid (PFOA), which causes a marked increase of the Acyl-CoA oxidase (ACOX) activity and no significant change in urate oxidase (UOX) activity...
March 2, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28237113/assays-to-monitor-pexophagy-in-yeast
#5
W Wang, S Subramani
Pexophagy is a selective autophagy process that degrades damaged and/or superfluous peroxisomes in the yeast vacuole or in mammalian lysosomes. The molecular mechanisms of pexophagy are well studied in yeast. Peroxisomes can be rapidly induced by oleate in the budding yeast, Saccharomyces cerevisiae, and by oleate or methanol in the methylotrophic yeast, Pichia pastoris. A number of peroxisomal matrix enzymes, such as 3-ketoacyl CoA thiolase (thiolase) and alcohol oxidase (AOX), are upregulated correspondingly to meet metabolic demands of the cells...
2017: Methods in Enzymology
https://www.readbyqxmd.com/read/28026986/xenophagy-a-battlefield-between-host-and-microbe-and-a-possible-avenue-for-cancer-treatment
#6
Kai Mao, Daniel J Klionsky
In eukaryotes, xenophagy is defined as a type of selective macroautophagy/autophagy that is used for eliminating invading pathogens. In contrast to other types of selective autophagy, such as mitophagy, pexophagy and ribophagy, xenophagy is used by eukaryotes for targeting microbes-hence the prefix "xeno" meaning "other" or "foreign"-that have infected a host cell, leading to their lysosomal degradation. This unique characteristic links xenophagy to antibacterial and antiviral defenses, as well as the immune response...
February 2017: Autophagy
https://www.readbyqxmd.com/read/27799409/acbd5-deficiency-causes-a-defect-in-peroxisomal-very-long-chain-fatty-acid-metabolism
#7
Sacha Ferdinandusse, Kim D Falkenberg, Janet Koster, Petra A Mooyer, Richard Jones, Carlo W T van Roermund, Amy Pizzino, Michael Schrader, Ronald J A Wanders, Adeline Vanderver, Hans R Waterham
BACKGROUND: Acyl-CoA binding domain containing protein 5 (ACBD5) is a peroxisomal membrane protein with a cytosolic acyl-CoA binding domain. Because of its acyl-CoA binding domain, ACBD5 has been assumed to function as an intracellular carrier of acyl-CoA esters. In addition, a role for ACBD5 in pexophagy has been suggested. However, the precise role of ACBD5 in peroxisomal metabolism and/or functioning has not yet been established. Previously, a genetic ACBD5 deficiency was identified in three siblings with retinal dystrophy and white matter disease...
October 31, 2016: Journal of Medical Genetics
https://www.readbyqxmd.com/read/27696999/aoatg26-a-putative-sterol-glucosyltransferase-is-required-for-autophagic-degradation-of-peroxisomes-mitochondria-and-nuclei-in-the-filamentous-fungus-aspergillus-oryzae
#8
Takashi Kikuma, Takayuki Tadokoro, Jun-Ichi Maruyama, Katsuhiko Kitamoto
Autophagy is a conserved process in eukaryotic cells for degradation of cellular proteins and organelles. In filamentous fungi, autophagic degradation of organelles such as peroxisomes, mitochondria, and nuclei occurs in basal cells after the prolonged culture, but its mechanism is not well understood. Here, we functionally analyzed the filamentous fungus Aspergillus oryzae AoAtg26, an ortholog of the sterol glucosyltransferase PpAtg26 involved in pexophagy in the yeast Pichia pastoris. Deletion of Aoatg26 caused a severe decrease in conidiation and aerial hyphae formation, which is typically observed in the autophagy-deficient A...
February 2017: Bioscience, Biotechnology, and Biochemistry
https://www.readbyqxmd.com/read/27605050/the-roles-of-%C3%AE-oxidation-and-cofactor-homeostasis-in-peroxisome-distribution-and-function-in-arabidopsis-thaliana
#9
Mauro A Rinaldi, Ashish B Patel, Jaeseok Park, Koeun Lee, Lucia C Strader, Bonnie Bartel
Key steps of essential metabolic pathways are housed in plant peroxisomes. We conducted a microscopy-based screen for anomalous distribution of peroxisomally targeted fluorescence in Arabidopsis thaliana This screen uncovered 34 novel alleles in 15 genes affecting oil body mobilization, fatty acid β-oxidation, the glyoxylate cycle, peroxisome fission, and pexophagy. Partial loss-of-function of lipid-mobilization enzymes conferred peroxisomes clustered around retained oil bodies without other notable defects, suggesting that this microscopy-based approach was sensitive to minor perturbations, and that fatty acid β-oxidation rates in wild type are higher than required for normal growth...
November 2016: Genetics
https://www.readbyqxmd.com/read/27597759/pex2-is-the-e3-ubiquitin-ligase-required-for-pexophagy-during-starvation
#10
Graeme Sargent, Tim van Zutphen, Tatiana Shatseva, Ling Zhang, Valeria Di Giovanni, Robert Bandsma, Peter Kijun Kim
Peroxisomes are metabolic organelles necessary for anabolic and catabolic lipid reactions whose numbers are highly dynamic based on the metabolic need of the cells. One mechanism to regulate peroxisome numbers is through an autophagic process called pexophagy. In mammalian cells, ubiquitination of peroxisomal membrane proteins signals pexophagy; however, the E3 ligase responsible for mediating ubiquitination is not known. Here, we report that the peroxisomal E3 ubiquitin ligase peroxin 2 (PEX2) is the causative agent for mammalian pexophagy...
September 12, 2016: Journal of Cell Biology
https://www.readbyqxmd.com/read/27556292/modnm1-dynamin-mediating-peroxisomal-and-mitochondrial-fission-in-complex-with-mofis1-and-momdv1-is-important-for-development-of-functional-appressorium-in-magnaporthe-oryzae
#11
Kaili Zhong, Xiao Li, Xinyi Le, Xiangyi Kong, Haifeng Zhang, Xiaobo Zheng, Ping Wang, Zhengguang Zhang
Dynamins are large superfamily GTPase proteins that are involved in various cellular processes including budding of transport vesicles, division of organelles, cytokinesis, and pathogen resistance. Here, we characterized several dynamin-related proteins from the rice blast fungus Magnaporthe oryzae and found that MoDnm1 is required for normal functions, including vegetative growth, conidiogenesis, and full pathogenicity. In addition, we found that MoDnm1 co-localizes with peroxisomes and mitochondria, which is consistent with the conserved role of dynamin proteins...
August 2016: PLoS Pathogens
https://www.readbyqxmd.com/read/27189367/yeast-peroxisomes-structure-functions-and-biotechnological-opportunities
#12
Andriy A Sibirny
Peroxisomes are ubiquitous organelles found in most eukaryotic cells. In yeasts, peroxisomes play important roles in cell metabolism, especially in different catabolic processes including fatty acid β-oxidation, the glyoxylic shunt and methanol metabolism, as well as some biosynthetic processes. In addition, peroxisomes are the compartment in which oxidases and catalase are localized. New peroxisomes mainly arise by fission of pre-existing ones, although they can also be formed from the endoplasmic reticulum (ER)...
June 2016: FEMS Yeast Research
https://www.readbyqxmd.com/read/27068951/autophagic-degradation-of-peroxisomes-in-mammals
#13
REVIEW
Zientara-Rytter Katarzyna, Subramani Suresh
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...
April 15, 2016: Biochemical Society Transactions
https://www.readbyqxmd.com/read/27050462/a-new-role-for-atm-in-selective-autophagy-of-peroxisomes-pexophagy
#14
Durga Nand Tripathi, Jiangwei Zhang, Ji Jing, Ruhee Dere, Cheryl Lyn Walker
Peroxisomes are autonomously replicating and highly metabolic organelles necessary for β-oxidation of fatty acids, a process that generates large amounts of reactive oxygen species (ROS). Maintaining a balance between biogenesis and degradation of peroxisomes is essential to maintain cellular redox balance, but how cells do this has remained somewhat of a mystery. While it is known that peroxisomes can be degraded via selective autophagy (pexophagy), little is known about how mammalian cells regulate pexophagy to maintain peroxisome homeostasis...
2016: Autophagy
https://www.readbyqxmd.com/read/26967755/the-peroxisome-as-a-cell-signaling-organelle
#15
REVIEW
Durga Nand Tripathi, Cheryl Lyn Walker
Peroxisomes participate in lipid metabolism, and are a major source of ROS in the cell. Their importance in cellular energy balance and redox homeostasis is well-established, as is the need to maintain peroxisome homeostasis to prevent pathologies associated with too few, or too many, of these organelles. How cells regulate peroxisome number has remained somewhat elusive. Recently, the tumor suppressors ATM and TSC, which regulate mTORC1 signaling, have been localized to peroxisomes. When activated by peroxisomal ROS, ATM signals to TSC to repress mTORC1 signaling and increase autophagic flux in cells, and also phosphorylates the peroxisomal protein PEX 5 to target peroxisomes for selective autophagy (pexophagy), providing a mechanism for regulation of peroxisomal homeostasis using ROS as a rheostat...
April 2016: Current Opinion in Cell Biology
https://www.readbyqxmd.com/read/26721431/2-2-dipyridyl-induces-pexophagy
#16
AiLin Jin, Joon No Lee, Min Soo Kim, SeongAe Kwak, Se-Jin Kim, Kyung Song, Seong-Kyu Choe, Raekil Park
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...
January 22, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/26542980/giant-peroxisomes-in-a-moss-physcomitrella-patens-peroxisomal-biogenesis-factor-11-mutant
#17
Yasuko Kamisugi, Shiro Mitsuya, Mahmoud El-Shami, Celia D Knight, Andrew C Cuming, Alison Baker
Peroxisomal biogenesis factor 11 (PEX11) proteins are found in yeasts, mammals and plants, and play a role in peroxisome morphology and regulation of peroxisome division. The moss Physcomitrella patens has six PEX11 isoforms which fall into two subfamilies, similar to those found in monocots and dicots. We carried out targeted gene disruption of the Phypa_PEX11-1 gene and compared the morphological and cellular phenotypes of the wild-type and mutant strains. The mutant grew more slowly and the development of gametophores was retarded...
January 2016: New Phytologist
https://www.readbyqxmd.com/read/26520587/beneficial-reward-to-risk-action-of-glucosamine-during-pathogenesis-of-osteoarthritis
#18
Yeon-Ho Kang, Sujeong Park, Chihyun Ahn, Jinsoo Song, Dongkyun Kim, Eun-Jung Jin
OBJECTIVE: Glucosamine is widely used to improve the symptoms and to delay the structural progression of osteoarthritis. However, its efficacy in osteoarthritis has been controversial and its underlying mechanism of action remains unclear. The aim of this study was to investigate the effects of glucosamine and the underlying mechanisms in human chondrocytes. METHODS: Chondrocytes from normal human articular cartilage were treated with glucosamine (10-100 mM). Subsequently, cell death was analyzed by Annexin V staining and FACS and mitochondrial function was studied by measuring the mitopotential...
October 31, 2015: European Journal of Medical Research
https://www.readbyqxmd.com/read/26458245/a-mammalian-pexophagy-target
#19
COMMENT
Suresh Subramani
Protein ubiquitylation in mammals is known to trigger selective autophagy of peroxisomes through a process termed pexophagy. The physiological peroxisomal target for pexophagy-related ubiquitylation has been controversial, but two studies have now identified the protein PEX5 as the real candidate.
November 2015: Nature Cell Biology
https://www.readbyqxmd.com/read/26453011/pexophagy-is-induced-by-increasing-peroxisomal-reactive-oxygen-species-in-1-10-phenanthroline-treated-cells
#20
Doo Sin Jo, Dong-Jun Bae, So Jung Park, Hae Mi Seo, Han Byeol Kim, Jeong Su Oh, Jong Wook Chang, Sang-Yeob Kim, Jung-Won Shin, Dong-Hyung Cho
Although autophagy regulates the quality and quantity of cellular organelles, the regulatory mechanisms of peroxisomal autophagy remain largely unknown. In this study, we developed a cell-based image screening assay, and identified 1,10-phenanthroline (Phen) as a novel pexophagy inducer from chemical library screening. Treatment with Phen induces selective loss of peroxisomes but not endoplasmic reticulum and Golgi apparatus in hepatocytes. In addition, Phen increases autophagic engulfment of peroxisomes in an ATG5 dependent manner...
November 13, 2015: Biochemical and Biophysical Research Communications
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