Masaaki Komatsu

Summary

Country: Japan

Publications

  1. doi request reprint Physiological significance of selective degradation of p62 by autophagy
    Masaaki Komatsu
    Laboratory of Frontier Science, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan
    FEBS Lett 584:1374-8. 2010
  2. pmc Persistent activation of Nrf2 through p62 in hepatocellular carcinoma cells
    Yoshihiro Inami
    Protein Metabolism Project, Tokyo Metropolitan Institute of Medical Science, Setagaya Ku, Tokyo 156 8501, Japan
    J Cell Biol 193:275-84. 2011
  3. pmc Macroautophagy deficiency mediates age-dependent neurodegeneration through a phospho-tau pathway
    Keiichi Inoue
    Departments of Pathology and Neurology, Taub Institute, Columbia University Medical Center, New York, NY 10032, USA
    Mol Neurodegener 7:48. 2012
  4. doi request reprint p62/SQSTM1/A170: physiology and pathology
    Masaaki Komatsu
    Protein Metabolism Project, Tokyo Metropolitan Institute of Medical Science, Setagaya Ku, Tokyo 156 8506, Japan
    Pharmacol Res 66:457-62. 2012
  5. doi request reprint Liver autophagy: physiology and pathology
    Masaaki Komatsu
    Protein Metabolism Project, Tokyo Metropolitan Institute of Medical Science, Tokyo 156 8506, Japan
    J Biochem 152:5-15. 2012
  6. ncbi request reprint Potential role of p62 in tumor development
    Masaaki Komatsu
    Protein Metabolism Project, Tokyo Metropolitan Institute of Medical Science, Setagaya Ku, Tokyo, Japan
    Autophagy 7:1088-90. 2011
  7. doi request reprint The selective autophagy substrate p62 activates the stress responsive transcription factor Nrf2 through inactivation of Keap1
    Masaaki Komatsu
    Laboratory of Frontier Science, Tokyo Metropolitan Institute of Medical Science, Bunkyo ku, Tokyo 113 8613, Japan
    Nat Cell Biol 12:213-23. 2010
  8. ncbi request reprint Selective autophagy regulates various cellular functions
    Masaaki Komatsu
    Tokyo Metropolitan Institute of Medical Science, Setagaya Ku, Japan
    Genes Cells 15:923-33. 2010
  9. ncbi request reprint Homeostatic levels of p62 control cytoplasmic inclusion body formation in autophagy-deficient mice
    Masaaki Komatsu
    Laboratory of Frontier Science, Tokyo Metropolitan Institute of Medical Science, Bunkyo ku, Tokyo 113 8613, Japan
    Cell 131:1149-63. 2007
  10. pmc The Atg8 conjugation system is indispensable for proper development of autophagic isolation membranes in mice
    Yu 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

Detail Information

Publications45

  1. doi request reprint Physiological significance of selective degradation of p62 by autophagy
    Masaaki 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...
  2. pmc Persistent activation of Nrf2 through p62 in hepatocellular carcinoma cells
    Yoshihiro 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...
  3. pmc Macroautophagy deficiency mediates age-dependent neurodegeneration through a phospho-tau pathway
    Keiichi Inoue
    Departments of Pathology and Neurology, Taub Institute, Columbia University Medical Center, New York, NY 10032, USA
    Mol Neurodegener 7:48. 2012
    ..Here we describe mice deficient in an essential macroautophagy component, Atg7, specifically within postnatal CNS neurons...
  4. doi request reprint p62/SQSTM1/A170: physiology and pathology
    Masaaki 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...
  5. doi request reprint Liver autophagy: physiology and pathology
    Masaaki 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...
  6. ncbi request reprint Potential role of p62 in tumor development
    Masaaki 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...
  7. doi request reprint The selective autophagy substrate p62 activates the stress responsive transcription factor Nrf2 through inactivation of Keap1
    Masaaki Komatsu
    Laboratory of Frontier Science, Tokyo Metropolitan Institute of Medical Science, Bunkyo ku, Tokyo 113 8613, Japan
    Nat Cell Biol 12:213-23. 2010
    ....
  8. ncbi request reprint Selective autophagy regulates various cellular functions
    Masaaki 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...
  9. ncbi request reprint Homeostatic levels of p62 control cytoplasmic inclusion body formation in autophagy-deficient mice
    Masaaki Komatsu
    Laboratory of Frontier Science, Tokyo Metropolitan Institute of Medical Science, Bunkyo ku, Tokyo 113 8613, Japan
    Cell 131:1149-63. 2007
    ....
  10. pmc The Atg8 conjugation system is indispensable for proper development of autophagic isolation membranes in mice
    Yu 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...
  11. doi request reprint Phosphorylation of p62 activates the Keap1-Nrf2 pathway during selective autophagy
    Yoshinobu Ichimura
    Protein Metabolism Project, Tokyo Metropolitan Institute of Medical Science, Tokyo 156 8506, Japan
    Mol Cell 51:618-31. 2013
    ..These results demonstrate that selective autophagy and the Keap1-Nrf2 pathway are interdependent, and that inhibitors of the interaction between phosphorylated p62 and Keap1 have potential as therapeutic agents against human HCC. ..
  12. ncbi request reprint Loss of autophagy in the central nervous system causes neurodegeneration in mice
    Masaaki 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...
  13. pmc p62/SQSTM1 cooperates with Parkin for perinuclear clustering of depolarized mitochondria
    Kei 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...
  14. pmc The Ufm1-activating enzyme Uba5 is indispensable for erythroid differentiation in mice
    Kanako 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...
  15. pmc Liver autophagy contributes to the maintenance of blood glucose and amino acid levels
    Junji 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...
  16. ncbi request reprint Loss of Pten, a tumor suppressor, causes the strong inhibition of autophagy without affecting LC3 lipidation
    Takashi 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...
  17. pmc A novel type of E3 ligase for the Ufm1 conjugation system
    Kanako 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...
  18. pmc Impairment of starvation-induced and constitutive autophagy in Atg7-deficient mice
    Masaaki 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...
  19. pmc PINK1 autophosphorylation upon membrane potential dissipation is essential for Parkin recruitment to damaged mitochondria
    Kei 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...
  20. ncbi request reprint Comprehensive proteomics analysis of autophagy-deficient mouse liver
    Naomi 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...
  21. ncbi request reprint Excess peroxisomes are degraded by autophagic machinery in mammals
    Jun 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...
  22. doi request reprint Loss of autophagy promotes murine acetaminophen hepatotoxicity
    Yuki 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...
  23. pmc A novel protein-conjugating system for Ufm1, a ubiquitin-fold modifier
    Masaaki 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...
  24. pmc PAC1 gene knockout reveals an essential role of chaperone-mediated 20S proteasome biogenesis and latent 20S proteasomes in cellular homeostasis
    Katsuhiro 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...
  25. ncbi request reprint Autophagy and neurodegeneration
    Masaaki 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...
  26. ncbi request reprint LC3B is indispensable for selective autophagy of p62 but not basal autophagy
    Yoko Maruyama
    Protein Metabolism Project, Tokyo Metropolitan Institute of Medical Science, Tokyo 156 8506, Japan Department of Pediatrics, School of Medicine, Keio University, Tokyo 160 8582, Japan
    Biochem Biophys Res Commun 446:309-15. 2014
    ..Our results suggest that while mammalian Atg8 homologs are functionally redundant with regard to autophagosome formation, selective autophagy is regulated by specific Atg8 homologs...
  27. doi request reprint Dissection of the role of p62/Sqstm1 in activation of Nrf2 during xenophagy
    Ryosuke Ishimura
    Protein Metabolism Project, Tokyo Metropolitan Institute of Medical Science, Tokyo 156 8506, Japan
    FEBS Lett 588:822-8. 2014
    ..Our data reveal the sequential dynamics of p62/Sqstm1 in response to bacterial infection. ..
  28. ncbi request reprint [Study on pathophysiology of autophagy]
    Masaaki Komatsu
    Department of Biochemistry, Juntendo University School of Medicine, 2 1 1 Hongo, Bunkyo ku, Tokyo 113 8421, Japan
    Seikagaku 79:749-60. 2007
  29. doi request reprint The FAP motif within human ATG7, an autophagy-related E1-like enzyme, is essential for the E2-substrate reaction of LC3 lipidation
    Isei 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...
  30. ncbi request reprint Selective turnover of p62/A170/SQSTM1 by autophagy
    Yoshinobu Ichimura
    Department of Biochemistry, Juntendo University School of Medicine, Bunkyo ku, Tokyo, Japan
    Autophagy 4:1063-6. 2008
    ....
  31. doi request reprint Autophagy is important in islet homeostasis and compensatory increase of beta cell mass in response to high-fat diet
    Chie 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...
  32. doi request reprint Method for monitoring pexophagy in mammalian cells
    Junji 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...
  33. ncbi request reprint [Autophagic-lysosomal system: physiology and pathology]
    Masaaki Komatsu
    Department of Biochemistry, Juntendo University School of Medicine, Bunkyo ku, Tokyo 113 8421, Japan
    Nihon Shinkei Seishin Yakurigaku Zasshi 26:75-81. 2006
    ..These results indicate the important role of autophagy in starvation response and the quality control of proteins and organelles in quiescent cells...
  34. doi request reprint Suppression of autophagy sensitizes Kupffer cells to endotoxin
    Hiroo 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...
  35. pmc Disrupted autophagy leads to dopaminergic axon and dendrite degeneration and promotes presynaptic accumulation of α-synuclein and LRRK2 in the brain
    Lauren 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...
  36. ncbi request reprint Pathophysiological role of autophagy: lesson from autophagy-deficient mouse models
    Yoshinobu 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...
  37. pmc PINK1 stabilized by mitochondrial depolarization recruits Parkin to damaged mitochondria and activates latent Parkin for mitophagy
    Noriyuki 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...
  38. doi request reprint Selective degradation of p62 by autophagy
    Yoshinobu 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...
  39. ncbi request reprint [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)...
  40. doi request reprint Discovery of Atg5/Atg7-independent alternative macroautophagy
    Yuya 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...
  41. doi request reprint Crucial role for autophagy in degranulation of mast cells
    Hiroko 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...
  42. ncbi request reprint Transient increase in proteinuria, poly-ubiquitylated proteins and ER stress markers in podocyte-specific autophagy-deficient mice following unilateral nephrectomy
    Juan Alejandro Oliva Trejo
    Division of Nephrology, Department of Internal Medicine, Juntendo University School of Medicine, 2 1 1 Hongo, Bunkyo ku, Tokyo 113 8421, Japan
    Biochem Biophys Res Commun 446:1190-6. 2014
    ..These results show the importance of the autophagic process in podocytes for maintaining a normal degree of filtration function during the adaptation to compensatory kidney hypertrophy following unilateral nephrectomy...
  43. doi request reprint Intermittent-hypoxia induced autophagy attenuates contractile dysfunction and myocardial injury in rat heart
    Hideyuki Maeda
    Department of Forensic Medicine, Graduate School of Medicine, The University of Tokyo, 7 3 1 Hongo, Bunkyo ku, Tokyo 113 0033, Japan
    Biochim Biophys Acta 1832:1159-66. 2013
    ..General significance. This study highlighted the potential implications of autophagy in cardio-protection in early SAS patients without comorbidity, reproduced in normal rats by 3~4weeks of IH...
  44. ncbi request reprint 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 hApg5p
    Isei 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...
  45. pmc Impaired autophagy in neurons after disinhibition of mammalian target of rapamycin and its contribution to epileptogenesis
    John 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...