Research Topics
Genomes and Genes
| Masaaki KomatsuSummaryCountry: Japan Publications
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Detail Information
Publications
Physiological significance of selective degradation of p62 by autophagyMasaaki Komatsu
Laboratory of Frontier Science, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan
FEBS Lett 584:1374-8. 2010..In this review, we introduce the selective turnover of the ubiquitin- and LC3-binding protein 'p62' through autophagy and discuss its physiological significance...
p62/SQSTM1/A170: physiology and pathologyMasaaki Komatsu
Protein Metabolism Project, Tokyo Metropolitan Institute of Medical Science, Setagaya Ku, Tokyo 156 8506, Japan
Pharmacol Res 66:457-62. 2012..In this review, we discuss the pathophysiological significance of p62 and its role in autophagy...
Liver autophagy: physiology and pathologyMasaaki Komatsu
Protein Metabolism Project, Tokyo Metropolitan Institute of Medical Science, Tokyo 156 8506, Japan
J Biochem 152:5-15. 2012..This review summarizes the physiologic roles of autophagy with a particular focus on liver autophagy based on analyses of knockout mice lacking Atg genes...
The selective autophagy substrate p62 activates the stress responsive transcription factor Nrf2 through inactivation of Keap1Masaaki Komatsu
Laboratory of Frontier Science, Tokyo Metropolitan Institute of Medical Science, Bunkyo ku, Tokyo 113 8613, Japan
Nat Cell Biol 12:213-23. 2010....
Selective autophagy regulates various cellular functionsMasaaki Komatsu
Tokyo Metropolitan Institute of Medical Science, Setagaya Ku, Japan
Genes Cells 15:923-33. 2010..Such selectivity allows diverse cellular regulation, similar to the ubiquitin proteasome pathway. In this review, we discuss the physiological roles of selective autophagy and their molecular mechanisms...
Potential role of p62 in tumor developmentMasaaki Komatsu
Protein Metabolism Project, Tokyo Metropolitan Institute of Medical Science, Setagaya Ku, Tokyo, Japan
Autophagy 7:1088-90. 2011..Recently, we identified the role of p62-positive aggregates in human HCC and autophagy-deficient tumors in tumor development through persistent activation of Nrf2, a transcription factor responsible for stress response...
The Atg8 conjugation system is indispensable for proper development of autophagic isolation membranes in miceYu Shin Sou
Laboratory of Frontier Science, Tokyo Metropolitan Institute of Medical Science, Bunkyo ku, Tokyo 113 8613, Japan
Mol Biol Cell 19:4762-75. 2008..The results indicate the essential role of the Atg8 system in the proper development of autophagic isolation membranes in mice...
Homeostatic levels of p62 control cytoplasmic inclusion body formation in autophagy-deficient miceMasaaki Komatsu
Laboratory of Frontier Science, Tokyo Metropolitan Institute of Medical Science, Bunkyo ku, Tokyo 113 8613, Japan
Cell 131:1149-63. 2007....
Loss of autophagy in the central nervous system causes neurodegeneration in miceMasaaki Komatsu
Laboratory of Frontier Science, Tokyo Metropolitan Institute of Medical Science, Bunkyo ku, Tokyo 113 8613, Japan
Nature 441:880-4. 2006..Our results indicate that autophagy is essential for the survival of neural cells, and that impairment of autophagy is implicated in the pathogenesis of neurodegenerative disorders involving ubiquitin-containing inclusion bodies...
The Ufm1-activating enzyme Uba5 is indispensable for erythroid differentiation in miceKanako Tatsumi
Protein Metabolism Project, Tokyo Metropolitan Institute of Medical Science, Kamikitazawa 2 1 6, Setagaya Ku, Tokyo 156 8506, Japan
Nat Commun 2:181. 2011..Our results suggest that one of the ubiquitin-like protein modification systems, the Ufm1 system, is involved in the regulation of haematopoiesis...
p62/SQSTM1 cooperates with Parkin for perinuclear clustering of depolarized mitochondriaKei Okatsu
Laboratory of Protein Metabolism, Tokyo Metropolitan Institute of Medical Science, Setagaya Ku, Tokyo 156 8506, Japan
Genes Cells 15:887-900. 2010..Thus, p62 is required for ubiquitylation-dependent clustering of damaged mitochondria, which resembles p62-mediated 'aggresome' formation of misfolded/unfolded proteins after ubiquitylation...
Liver autophagy contributes to the maintenance of blood glucose and amino acid levelsJunji Ezaki
Department of Biochemistry, Juntendo University School of Medicine, Bunkyo ku, Tokyo, Japan
Autophagy 7:727-36. 2011..This indicates that insulin plays a dominant role over glucagon in controlling liver autophagy. These results are the first to show that liver-specific autophagy plays a role in blood glucose regulation...
Impairment of starvation-induced and constitutive autophagy in Atg7-deficient miceMasaaki Komatsu
Department of Molecular Oncology, Tokyo Metropolitan Institute of Medical Science, Bunkyo ku, Tokyo 113 8613, Japan
J Cell Biol 169:425-34. 2005..Our results indicate the important role of autophagy in starvation response and the quality control of proteins and organelles in quiescent cells...
A novel type of E3 ligase for the Ufm1 conjugation systemKanako Tatsumi
Laboratory of Frontier Science, Tokyo Metropolitan Institute of Medical Science, Setagaya Ku, Tokyo 156 8506, Japan
J Biol Chem 285:5417-27. 2010..Intriguingly, immunological analysis revealed localizations of Ufl1 and C20orf116 mainly to the endoplasmic reticulum. Our results provide novel insights into the Ufm1 system involved in cellular regulation of multicellular organisms...
PINK1 autophosphorylation upon membrane potential dissipation is essential for Parkin recruitment to damaged mitochondriaKei Okatsu
Laboratory of Protein Metabolism, Tokyo Metropolitan Institute of Medical Science, Setagaya Ku, 156 8506, Japan
Nat Commun 3:1016. 2012..We propose that autophosphorylation of Ser228 and Ser402 in PINK1 is essential for efficient mitochondrial localization of Parkin...
Persistent activation of Nrf2 through p62 in hepatocellular carcinoma cellsYoshihiro Inami
Protein Metabolism Project, Tokyo Metropolitan Institute of Medical Science, Setagaya Ku, Tokyo 156 8501, Japan
J Cell Biol 193:275-84. 2011..These results indicate the involvement of persistent activation of Nrf2 through the accumulation of p62 in hepatoma development...
Loss of Pten, a tumor suppressor, causes the strong inhibition of autophagy without affecting LC3 lipidationTakashi Ueno
The Department of Biochemistry, Juntendo University School of Medicine, Hongo, Tokyo, Japan
Autophagy 4:692-700. 2008..Collectively, we conclude that enhanced insulin signaling in Pten deficiency suppresses autophagy at the formation and maturation steps of autophagosomes, without inhibiting ATG conjugation reactions...
Comprehensive proteomics analysis of autophagy-deficient mouse liverNaomi Matsumoto
Department of Biochemistry, Juntendo University School of Medicine, 2 1 1 Hongo Bunkyo ku, Tokyo, Japan
Biochem Biophys Res Commun 368:643-9. 2008..Our results suggest that autophagy deficiency causes oxidative stress, and such stress might be the main cause of liver injury in autophagy-deficient liver...
Loss of autophagy promotes murine acetaminophen hepatotoxicityYuki Igusa
Department of Gastroenterology, Juntendo University School of Medicine, Hongo 2 1 1, Bunkyo ku, Tokyo 113 8421, Japan
J Gastroenterol 47:433-43. 2012..The aim of this study was to clarify if autophagy is linked to liver injury due to acetaminophen...
PAC1 gene knockout reveals an essential role of chaperone-mediated 20S proteasome biogenesis and latent 20S proteasomes in cellular homeostasisKatsuhiro Sasaki
Laboratory of Frontier Science, Core Technology and Research Center, Tokyo Metropolitan Institute of Medical Science, Setagayaku, Tokyo, Japan
Mol Cell Biol 30:3864-74. 2010..They also accumulated ubiquitinated proteins and exhibited premature senescence. Our results demonstrate the importance of the PAC1-dependent assembly pathway and of the latent 20S proteasomes for maintaining cellular integrity...
A novel protein-conjugating system for Ufm1, a ubiquitin-fold modifierMasaaki Komatsu
Department of Molecular Oncology, Tokyo Metropolitan Institute of Medical Science, Bunkyo ku, Tokyo, Japan
EMBO J 23:1977-86. 2004..Ufm1, Uba5, and Ufc1 are all conserved in metazoa and plants but not in yeast, suggesting its potential roles in various multicellular organisms...
Autophagy and neurodegenerationMasaaki Komatsu
Laboratory of Frontier Science, Tokyo Metropolitan Institute of Medical Science, Bunkyo-ku, Tokyo, Japan
Autophagy 2:315-7. 2006..Here we discuss the consequences of autophagy deficiency in neurons...
The FAP motif within human ATG7, an autophagy-related E1-like enzyme, is essential for the E2-substrate reaction of LC3 lipidationIsei Tanida
Department of Biochemistry and Cell Biology, National Institute of Infectious Diseases, Tokyo, Japan
Autophagy 8:88-97. 2012..These results indicated that the FAP motif of ATG7 is indispensable for formation of the ATG3-LC3 E2-substrate intermediate through the interaction of ATG7 with ATG3...
Selective turnover of p62/A170/SQSTM1 by autophagyYoshinobu Ichimura
Department of Biochemistry, Juntendo University School of Medicine, Bunkyo ku, Tokyo, Japan
Autophagy 4:1063-6. 2008....
Autophagy is important in islet homeostasis and compensatory increase of beta cell mass in response to high-fat dietChie Ebato
Department of Medicine, Endocrinology, and Metabolism, Juntendo University School of Medicine, 2 1 1 Hongo, Bunkyo ku, Tokyo 113 8421, Japan
Cell Metab 8:325-32. 2008..The results also identified a unique role for inductive autophagy as an adaptive response of beta cells in the presence of insulin resistance induced by high-fat diet...
Method for monitoring pexophagy in mammalian cellsJunji Ezaki
Department of Biochemistry, Juntendo University School of Medicine, Hongo, Tokyo, Japan
Methods Enzymol 452:215-26. 2009..Although most of the excess peroxisomes in the liver are selectively degraded within one week, this rapid removal is exclusively impaired in the autophagy-deficient liver...
Excess peroxisomes are degraded by autophagic machinery in mammalsJun-ichi Iwata
Department of Biochemistry, Juntendo University School of Medicine, Bunkyo-ku, Tokyo, Japan
J Biol Chem 281:4035-41. 2006..This is the first direct evidence for the contribution of autophagic machinery in peroxisomal degradation in mammals...
Suppression of autophagy sensitizes Kupffer cells to endotoxinHiroo Fukada
Department of Gastroenterology, Juntendo University School of Medicine Protein Metabolism Project, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan
Hepatol Res 42:1112-8. 2012..Conclusion: These results suggest that suppression of autophagy observed in Kupffer cells from steatotic liver sensitizes to endotoxin. In conclusion, suppression of autophagy may play a pivotal role on progression of NAFLD...
Disrupted autophagy leads to dopaminergic axon and dendrite degeneration and promotes presynaptic accumulation of α-synuclein and LRRK2 in the brainLauren G Friedman
Department of Neurology, Friedman Brain Institute, Mount Sinai School of Medicine, New York, NY 10029, USA
J Neurosci 32:7585-93. 2012..Our findings implicate dysfunctional autophagy as one of the failing cellular mechanisms involved in the pathogenesis of idiopathic PD...
Pathophysiological role of autophagy: lesson from autophagy-deficient mouse modelsYoshinobu Ichimura
Protein Metabolism Project, Tokyo Metropolitan Institute of Medical ScienceSetagaya ku, Tokyo 156 8501, Japan
Exp Anim 60:329-45. 2011..Herein, we introduce pathophysiological roles of starvation-induced, constitutive, and selective autophagy (in particular, selective turnover of p62 through autophagy) disclosed by autophagy-deficient mouse models...
Selective degradation of p62 by autophagyYoshinobu Ichimura
Protein Metabolism Project, Tokyo Metropolitan Institute of Medical Science, Setagaya Ku, Tokyo 156 8506, Japan
Semin Immunopathol 32:431-6. 2010..In this review, we discuss the physiological roles of the selective turnover of p62 by autophagy and their molecular mechanisms...
PINK1 stabilized by mitochondrial depolarization recruits Parkin to damaged mitochondria and activates latent Parkin for mitophagyNoriyuki Matsuda
Laboratory of Frontier Science, Tokyo Metropolitan Institute of Medical Science, Setagaya Ku, Tokyo 156 8506, Japan
J Cell Biol 189:211-21. 2010..Some pathogenic mutations of PINK1 and Parkin interfere with the aforementioned events, suggesting an etiological importance. These results provide crucial insight into the pathogenic mechanisms of PD...
[Role of mitophagy in hereditary Parkinson's disease]Noriyuki Matsuda
Laboratory of Protein Metabolism, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan
Brain Nerve 64:279-85. 2012..Here we provide an overview of how PINK1 and Parkin identify, label and clear damaged/depolarized mitochondria, focusing on the role of mitochondrial autophagy (mitophagy)...
Discovery of Atg5/Atg7-independent alternative macroautophagyYuya Nishida
Department of Pathological Cell Biology, Medical Research Institute, Tokyo Medical and Dental University, 1 5 45 Yushima, Bunkyo ku, Tokyo 113 8510, Japan
Nature 461:654-8. 2009..These results indicate that mammalian macroautophagy can occur through at least two different pathways: an Atg5/Atg7-dependent conventional pathway and an Atg5/Atg7-independent alternative pathway...
Crucial role for autophagy in degranulation of mast cellsHiroko Ushio
Atopy Allergy Research Center, Juntendo University School of Medicine, Bunkyo ku, Tokyo, Japan
J Allergy Clin Immunol 127:1267-76.e6. 2011..However, a role for autophagy in development and/or function of mast cells is unknown...
Human Apg3p/Aut1p homologue is an authentic E2 enzyme for multiple substrates, GATE-16, GABARAP, and MAP-LC3, and facilitates the conjugation of hApg12p to hApg5pIsei Tanida
Department of Biochemistry, Juntendo University School of Medicine, 2 1 1, Hongo, Bunkyo ku, Tokyo 113 8421, Japan
J Biol Chem 277:13739-44. 2002..Furthermore, hApg3p coimmunoprecipitates with hApg12p, and the overexpression of hApg3p facilitates the formation of the GFPhApg12p.thApg5p conjugate, suggesting that hApg3p cross-talks with the hApg12p conjugation system...
Impaired autophagy in neurons after disinhibition of mammalian target of rapamycin and its contribution to epileptogenesisJohn McMahon
Center for Neuropharmacology and Neuroscience, Albany Medical College, Albany, New York 12208, USA
J Neurosci 32:15704-14. 2012..Thus, our study suggests that impaired autophagy contributes to epileptogenesis, which may be of interest as a potential therapeutic target for epilepsy treatment and/or prevention...
