Noboru Mizushima

Summary

Affiliation: Tokyo Medical and Dental University
Country: Japan

Publications

  1. doi Physiological functions of autophagy
    Noboru Mizushima
    Department of Physiology and Cell Biology, Tokyo Medical and Dental University, Tokyo 113 8519, Japan
    Curr Top Microbiol Immunol 335:71-84. 2009
  2. pmc Autophagy in mammalian development and differentiation
    Noboru Mizushima
    Department of Physiology and Cell Biology, Tokyo Medical and Dental University, Tokyo 113 8519, Japan
    Nat Cell Biol 12:823-30. 2010
  3. ncbi Autophagy: process and function
    Noboru Mizushima
    Department of Physiology and Cell Biology, Tokyo Medical and Dental University, Tokyo 113 8519, Japan
    Genes Dev 21:2861-73. 2007
  4. ncbi How to interpret LC3 immunoblotting
    Noboru Mizushima
    Department of Physiology and Cell Biology, Tokyo Medical and Dental University, Tokyo, Japan
    Autophagy 3:542-5. 2007
  5. pmc Mitochondrial dysfunction associated with increased oxidative stress and α-synuclein accumulation in PARK2 iPSC-derived neurons and postmortem brain tissue
    Yoichi Imaizumi
    Department of Physiology, Keio University School of Medicine, 35 Shinanomachi, Tokyo 160 8582, Japan
    Mol Brain 5:35. 2012
  6. doi Autophagy: renovation of cells and tissues
    Noboru Mizushima
    Department of Physiology and Cell Biology, Tokyo Medical and Dental University, Tokyo 113 8519, Japan
    Cell 147:728-41. 2011
  7. doi Autophagy in protein and organelle turnover
    N Mizushima
    Department of Physiology and Cell Biology, Tokyo Medical and Dental University, 1 5 45 Yushima, Bunkyo ku, Tokyo 113 8519, Japan
    Cold Spring Harb Symp Quant Biol 76:397-402. 2011
  8. pmc Methods in mammalian autophagy research
    Noboru Mizushima
    Department of Physiology and Cell Biology, Tokyo Medical and Dental University, Tokyo 113 8519, Japan
    Cell 140:313-26. 2010
  9. doi The role of the Atg1/ULK1 complex in autophagy regulation
    Noboru Mizushima
    Department of Physiology and Cell Biology, Tokyo Medical and Dental University, Tokyo 113 8519, Japan
    Curr Opin Cell Biol 22:132-9. 2010
  10. doi The role of Atg proteins in autophagosome formation
    Noboru Mizushima
    Department of Physiology and Cell Biology, Tokyo Medical and Dental University, Tokyo 113 8519, Japan
    Annu Rev Cell Dev Biol 27:107-32. 2011

Detail Information

Publications98

  1. doi Physiological functions of autophagy
    Noboru Mizushima
    Department of Physiology and Cell Biology, Tokyo Medical and Dental University, Tokyo 113 8519, Japan
    Curr Top Microbiol Immunol 335:71-84. 2009
    ..This review summarizes the physiological roles of autophagy in amino acid pool maintenance, intracellular quality control, development, cell death, tumor suppression and anti-aging...
  2. pmc Autophagy in mammalian development and differentiation
    Noboru Mizushima
    Department of Physiology and Cell Biology, Tokyo Medical and Dental University, Tokyo 113 8519, Japan
    Nat Cell Biol 12:823-30. 2010
    ..Here we review the main advances in our understanding of these functions...
  3. ncbi Autophagy: process and function
    Noboru Mizushima
    Department of Physiology and Cell Biology, Tokyo Medical and Dental University, Tokyo 113 8519, Japan
    Genes Dev 21:2861-73. 2007
    ..In this review, the process of autophagy is summarized, and the role of autophagy is discussed in a process-based manner...
  4. ncbi How to interpret LC3 immunoblotting
    Noboru Mizushima
    Department of Physiology and Cell Biology, Tokyo Medical and Dental University, Tokyo, Japan
    Autophagy 3:542-5. 2007
    ..Accordingly, simple comparison of LC3-I and LC3-II, or summation of LC3-I and LC3-II for ratio determinations, may not be appropriate, and rather, the amount of LC3-II can be compared between samples...
  5. pmc Mitochondrial dysfunction associated with increased oxidative stress and α-synuclein accumulation in PARK2 iPSC-derived neurons and postmortem brain tissue
    Yoichi Imaizumi
    Department of Physiology, Keio University School of Medicine, 35 Shinanomachi, Tokyo 160 8582, Japan
    Mol Brain 5:35. 2012
    ..The familial form of PD, PARK2, is caused by mutations in the parkin gene. parkin-knockout mouse models show some abnormalities, but they do not fully recapitulate the pathophysiology of human PARK2...
  6. doi Autophagy: renovation of cells and tissues
    Noboru Mizushima
    Department of Physiology and Cell Biology, Tokyo Medical and Dental University, Tokyo 113 8519, Japan
    Cell 147:728-41. 2011
    ....
  7. doi Autophagy in protein and organelle turnover
    N Mizushima
    Department of Physiology and Cell Biology, Tokyo Medical and Dental University, 1 5 45 Yushima, Bunkyo ku, Tokyo 113 8519, Japan
    Cold Spring Harb Symp Quant Biol 76:397-402. 2011
    ..In this review I describe the various roles of autophagy, with a particular focus on the turnover of cytoplasmic proteins and organelles...
  8. pmc Methods in mammalian autophagy research
    Noboru Mizushima
    Department of Physiology and Cell Biology, Tokyo Medical and Dental University, Tokyo 113 8519, Japan
    Cell 140:313-26. 2010
    ..In this Primer, we discuss methods to monitor autophagy and to modulate autophagic activity, with a primary focus on mammalian macroautophagy...
  9. doi The role of the Atg1/ULK1 complex in autophagy regulation
    Noboru Mizushima
    Department of Physiology and Cell Biology, Tokyo Medical and Dental University, Tokyo 113 8519, Japan
    Curr Opin Cell Biol 22:132-9. 2010
    ..Furthermore, through studies of the Atg1/ULK1 complex, the molecular mechanism by which (m)TORC1 regulates autophagy is now being clarified in detail...
  10. doi The role of Atg proteins in autophagosome formation
    Noboru Mizushima
    Department of Physiology and Cell Biology, Tokyo Medical and Dental University, Tokyo 113 8519, Japan
    Annu Rev Cell Dev Biol 27:107-32. 2011
    ..In this review we describe the molecular mechanism of autophagosome formation with particular focus on the function of Atg proteins and the long-standing discussion regarding the origin of the autophagosome membrane...
  11. ncbi Intracellular quality control by autophagy: how does autophagy prevent neurodegeneration?
    Noboru Mizushima
    Department of Bioregulation and Metabolism, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan
    Autophagy 2:302-4. 2006
    ..Furthermore, the primary targets of autophagy are diffuse cytosolic proteins, not protein aggregates themselves...
  12. ncbi Protein turnover via autophagy: implications for metabolism
    Noboru Mizushima
    Department of Physiology and Cell Biology, Tokyo Medical and Dental University, Tokyo 113 8519, Japan
    Annu Rev Nutr 27:19-40. 2007
    ..We review the current information on the mechanism of autophagy, with a focus on its role in protein metabolism and intracellular homeostasis...
  13. pmc Nutrient-dependent mTORC1 association with the ULK1-Atg13-FIP200 complex required for autophagy
    Nao Hosokawa
    Department of Physiology and Cell Biology, Tokyo Medical and Dental University, Tokyo 113 8519, Japan
    Mol Biol Cell 20:1981-91. 2009
    ..ULK1 is dephosphorylated by rapamycin treatment or starvation. These data suggest that mTORC1 suppresses autophagy through direct regulation of the approximately 3-MDa ULK1-Atg13-FIP200 complex...
  14. pmc Tti1 and Tel2 are critical factors in mammalian target of rapamycin complex assembly
    Takeshi Kaizuka
    Department of Physiology and Cell Biology, Tokyo Medical and Dental University, Tokyo 113 8519, Japan
    J Biol Chem 285:20109-16. 2010
    ..These results indicate that Tti1 and Tel2 are important not only for mTOR stability but also for assembly of the mTOR complexes to maintain their activities...
  15. pmc p62 Targeting to the autophagosome formation site requires self-oligomerization but not LC3 binding
    Eisuke Itakura
    Department of Physiology and Cell Biology, Tokyo Medical and Dental University, Bunkyo ku, Tokyo, Japan
    J Cell Biol 192:17-27. 2011
    ..These results suggest that p62 localizes to the autophagosome formation site on the ER, where autophagosomes are nucleated. This process is similar to the yeast cytoplasm to vacuole targeting pathway...
  16. 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...
  17. ncbi 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
    ....
  18. pmc Characterization of autophagosome formation site by a hierarchical analysis of mammalian Atg proteins
    Eisuke Itakura
    Department of Physiology and Cell Biology, Tokyo Medical and Dental University, Bunkyo ku, Tokyo, Japan
    Autophagy 6:764-76. 2010
    ..These hierarchical analyses suggest that ULK1, Atg14 and VMP1 localize to the ER-associated autophagosome formation sites in a PI3-kinase activity-independent manner...
  19. pmc FIP200 regulates targeting of Atg16L1 to the isolation membrane
    Taki Nishimura
    Department of Physiology and Cell Biology, Tokyo Medical and Dental University, Tokyo 113 8519, Japan
    EMBO Rep 14:284-91. 2013
    ..Thus, FIP200 regulates not only early events but also late events of autophagosome formation through direct interaction with Atg16L1...
  20. doi Autophagy is essential for preimplantation development of mouse embryos
    Satoshi Tsukamoto
    Department of Physiology and Cell Biology, Tokyo Medical and Dental University, 1 5 45 Yushima, Bunkyo ku, Tokyo 113 8519, Japan
    Science 321:117-20. 2008
    ..Protein synthesis rates were reduced in the autophagy-null embryos. Thus, autophagic degradation within early embryos is essential for preimplantation development in mammals...
  21. pmc FIP200, a ULK-interacting protein, is required for autophagosome formation in mammalian cells
    Taichi Hara
    Department of Physiology and Cell Biology, Tokyo Medical and Dental University, Bunkyo ku, Tokyo 113 8549, Japan
    J Cell Biol 181:497-510. 2008
    ..These results suggest that FIP200 is a novel mammalian autophagy factor that functions together with ULKs...
  22. pmc Autophagy-deficient mice develop multiple liver tumors
    Akito Takamura
    Department of Physiology and Cell Biology, Tokyo Medical and Dental University, Tokyo 113 8519, Japan
    Genes Dev 25:795-800. 2011
    ..These results suggest that autophagy is important for the suppression of spontaneous tumorigenesis through a cell-intrinsic mechanism, particularly in the liver, and that p62 accumulation contributes to tumor progression...
  23. ncbi Role of ULK-FIP200 complex in mammalian autophagy: FIP200, a counterpart of yeast Atg17?
    Taichi Hara
    Department of Physiology and Cell Biology, Tokyo Medical and Dental University, Tokyo, Japan
    Autophagy 5:85-7. 2009
    ..Here, we discuss the role of the ULK-FIP200 complex in autophagy and the possibility that FIP200 functions as a mammalian counterpart of Atg17...
  24. 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...
  25. ncbi Dynein- and activity-dependent retrograde transport of autophagosomes in neuronal axons
    Kiyoshi Katsumata
    Department of Neurophysiology, School of Medicine, Keio University, Tokyo, Japan
    Autophagy 6:378-85. 2010
    ..These results suggest that autophagosomes play important roles in axons and are dynamically regulated under physiological and pathological conditions...
  26. doi The hairpin-type tail-anchored SNARE syntaxin 17 targets to autophagosomes for fusion with endosomes/lysosomes
    Eisuke Itakura
    Department of Physiology and Cell Biology, Tokyo Medical and Dental University, Tokyo 113 8519, Japan
    Cell 151:1256-69. 2012
    ..These findings reveal a mechanism by which the SNARE protein is available to the completed autophagosome...
  27. ncbi Suppression of basal autophagy in neural cells causes neurodegenerative disease in mice
    Taichi Hara
    Department of Bioregulation and Metabolism, Tokyo Metropolitan Institute of Medical Science, Tokyo 113 8613, Japan
    Nature 441:885-9. 2006
    ....
  28. ncbi The role of autophagy during the oocyte-to-embryo transition
    Satoshi Tsukamoto
    Department of Physiology and Cell Biology, Tokyo Medical and Dental University, Tokyo, Japan
    Autophagy 4:1076-8. 2008
    ..Thus, the degradation of maternal factors by autophagy is essential for preimplantation development in mammals...
  29. ncbi LC3, an autophagosome marker, can be incorporated into protein aggregates independent of autophagy: caution in the interpretation of LC3 localization
    Akiko Kuma
    Department of Physiology and Cell Biology, Tokyo Medical and Dental University, Tokyo, Japan
    Autophagy 3:323-8. 2007
    ..Therefore, LC3 localization should be carefully interpreted, particularly if LC3 is overexpressed by transient transfection or if aggregates are formed within cells...
  30. ncbi Aberrant membranes and double-membrane structures accumulate in the axons of Atg5-null Purkinje cells before neuronal death
    Jun Nishiyama
    Department of Physiology, School of Medicine, Keio University, Tokyo, Japan
    Autophagy 3:591-6. 2007
    ..These results suggest that Atg5 plays important roles in the maintenance of axon morphology and membrane structures, and its loss of function leads to the swelling of axons, followed by progressive neurodegeneration in mammalian neurons...
  31. ncbi Atg101, a novel mammalian autophagy protein interacting with Atg13
    Nao Hosokawa
    Department of Physiology and Cell Biology, Tokyo Medical and Dental University, Tokyo, Japan
    Autophagy 5:973-9. 2009
    ..Furthermore, Atg101 is important for the stability and basal phosphorylation of Atg13 and ULK1. These data suggest that Atg101 is a novel Atg protein that functions together with ULK, Atg13 and FIP200...
  32. doi Autophagosomes in GFP-LC3 Transgenic Mice
    Noboru Mizushima
    Department of Physiology and Cell Biology, Tokyo Medical and Dental University, Tokyo, Japan
    Methods Mol Biol 445:119-24. 2008
    ..To analyze autophagy in whole animals, we generated GFP-LC3 transgenic mice and describe here how we determine the occurrence of autophagy in vivo using this mouse model...
  33. doi A sensitive and quantitative technique for detecting autophagic events based on lysosomal delivery
    Hiroyuki Katayama
    Life Function and Dynamics, ERATO, JST, Bunkyo ku, Tokyo 113 8519, Japan
    Chem Biol 18:1042-52. 2011
    ....
  34. pmc Proteasome-dependent activation of mammalian target of rapamycin complex 1 (mTORC1) is essential for autophagy suppression and muscle remodeling following denervation
    Pham Nguyen Quy
    Department of Physiology and Cell Biology, Tokyo Medical and Dental University, Tokyo 113 8519, Japan
    J Biol Chem 288:1125-34. 2013
    ..These results suggest that denervation induces not only muscle degradation but also adaptive muscle response in a proteasome- and mTORC1-dependent manner...
  35. doi Structures containing Atg9A and the ULK1 complex independently target depolarized mitochondria at initial stages of Parkin-mediated mitophagy
    Eisuke Itakura
    Department of Physiology and Cell Biology, Tokyo Medical and Dental University, Tokyo 113 8519, Japan
    J Cell Sci 125:1488-99. 2012
    ..These findings suggest a process whereby the isolation membrane is generated de novo on damaged mitochondria as opposed to one where a preformed isolation membrane recognizes mitochondria...
  36. pmc Mammalian Atg2 proteins are essential for autophagosome formation and important for regulation of size and distribution of lipid droplets
    Anoop Kumar G Velikkakath
    Department of Physiology and Cell Biology, Tokyo Medical and Dental University, Tokyo 113 8519, Japan
    Mol Biol Cell 23:896-909. 2012
    ..These data suggest that mammalian Atg2 proteins function both in autophagosome formation and regulation of lipid droplet morphology and dispersion...
  37. pmc Beclin 1 forms two distinct phosphatidylinositol 3-kinase complexes with mammalian Atg14 and UVRAG
    Eisuke Itakura
    Department of Physiology and Cell Biology, Tokyo Medical and Dental University, Tokyo 113 8519, Japan
    Mol Biol Cell 19:5360-72. 2008
    ..These results suggest that mammalian cells have at least two distinct class III PI3-kinase complexes, which may function in different membrane trafficking pathways...
  38. ncbi Organelle degradation during the lens and erythroid differentiation is independent of autophagy
    Makoto Matsui
    Department of Bioregulation and Metabolism, The Tokyo Metropolitan Institute of Medical Science, Tokyo 113 8613, Japan
    Biochem Biophys Res Commun 339:485-9. 2006
    ..Our data suggest that degradation system(s) other than autophagy play major roles in organelle degradation during these processes...
  39. ncbi Chromosomal mapping of the GFP-LC3 transgene in GFP-LC3 mice
    Akiko Kuma
    Department of Physiology and Cell Biology, Tokyo Medical and Dental University, Tokyo, Japan SORST, Japan Science and Technology Agency, Kawaguchi, Japan
    Autophagy 4:61-2. 2008
    ..Homozygous GFP-LC3 mice (GFP-LC3(tg/tg)) were healthy, fertile and did not show an abnormal phenotype. Thus, GFP-LC3 integration in this model appears not to affect functions of other genes, justifying use of this mouse model...
  40. pmc Differential contribution of insulin and amino acids to the mTORC1-autophagy pathway in the liver and muscle
    Takako Naito
    Department of Physiology and Cell Biology, Tokyo Medical and Dental University, Tokyo 113 8519, Japan
    J Biol Chem 288:21074-81. 2013
    ..These results suggest that autophagy is differentially regulated by insulin and amino acids in a tissue-dependent manner. ..
  41. pmc Autophagy-related Atg8 localizes to the apicoplast of the human malaria parasite Plasmodium falciparum
    Kei Kitamura
    Department of Physiology and Cell Biology, Tokyo Medical and Dental University, Tokyo, Japan
    PLoS ONE 7:e42977. 2012
    ..These data suggest that, although Plasmodium parasites have lost most Atg proteins during evolution, they use the Atg8 conjugation system for the unique organelle, the apicoplast...
  42. doi A receptor for eating mitochondria
    Naotada Ishihara
    Department of Physiology and Cell Biology, Tokyo Medical and Dental University, Tokyo, Japan
    Dev Cell 17:1-2. 2009
    ..Using yeast genetics, a mitochondrial surface receptor involved in mitochondrial autophagy has recently been identified...
  43. pmc Autophagy fights disease through cellular self-digestion
    Noboru Mizushima
    Department of Physiology and Cell Biology, Tokyo Medical and Dental University, Tokyo 113 8519, Japan
    Nature 451:1069-75. 2008
    ..Understanding autophagy may ultimately allow scientists and clinicians to harness this process for the purpose of improving human health...
  44. doi [Aging and autophagy]
    Pham Nguyen Quy
    Department of Physiology and Cell Biology, Tokyo Medical and Dental University, Japan
    Clin Calcium 23:39-44. 2013
    ..Here, we review recent evidences in support of tight connections between autophagy and aging...
  45. pmc Deletion of autophagy-related 5 (Atg5) and Pik3c3 genes in the lens causes cataract independent of programmed organelle degradation
    Hideaki Morishita
    Department of Physiology and Cell Biology, Tokyo Medical and Dental University, Tokyo 113 8519, Japan
    J Biol Chem 288:11436-47. 2013
    ..Taken together, these results suggest that clearance of lens organelles is independent of macroautophagy. These findings also clarify the physiological role of Atg5 and Pik3c3 in quality control and development of the lens, respectively...
  46. doi Methods for monitoring autophagy using GFP-LC3 transgenic mice
    Noboru Mizushima
    Department of Physiology and Cell Biology, Tokyo Medical and Dental University, Tokyo, Japan
    Methods Enzymol 452:13-23. 2009
    ..This chapter describes the background and practicality of, and possible precautions in the application of, this method using the GFP-LC3 transgenic mouse model...
  47. pmc Parkin mediates proteasome-dependent protein degradation and rupture of the outer mitochondrial membrane
    Saori R Yoshii
    Department of Physiology and Cell Biology, Tokyo Medical and Dental University, Tokyo, Japan
    J Biol Chem 286:19630-40. 2011
    ..These results suggest that Parkin regulates degradation of outer and inner mitochondrial membrane proteins differently through proteasome- and mitophagy-dependent pathways...
  48. doi Physiological role of autophagy as an intracellular recycling system: with an emphasis on nutrient metabolism
    Akiko Kuma
    Department of Physiology and Cell Biology, Tokyo Medical and Dental University, 1 5 45 Yushima, Bunkyo ku, Tokyo 113 8519, Japan
    Semin Cell Dev Biol 21:683-90. 2010
    ..Here, we discuss the role of this catabolic pathway in recycling intracellular components, with particular reference to nutrient metabolism...
  49. ncbi Generation of cell lines with tetracycline-regulated autophagy and a role for autophagy in controlling cell size
    Nao Hosokawa
    Department of Bioregulation and Metabolism, Tokyo Metropolitan Institute of Medical Science, 3 18 22 Honkomagome, Tokyo 113 8613, Japan
    FEBS Lett 580:2623-9. 2006
    ..The generated cell lines will be useful reagents for future mechanistic studies into the regulation and physiologic significance of autophagy...
  50. ncbi [The role of autophagy in quality control inside neural cells]
    Noboru Mizushima
    Department of Physiology and Cell Biology, Tokyo Medical and Dental University
    Rinsho Shinkeigaku 46:885-6. 2006
    ..These data suggest that basal autophagy has a critical role in intracellular protein quality control under normal conditions, which is independent of the role of induced autophagy as an adaptation to starvation...
  51. pmc A(beta) generation in autophagic vacuoles
    Noboru Mizushima
    Department of Bioregulation and Metabolism, Tokyo Metropolitan Institute of Medical Science, Tokyo 113 8613, Japan
    J Cell Biol 171:15-7. 2005
    ..In this issue, Yu et al. (on p. 87) report a novel mechanism for the generation of Abeta peptides, which takes place in autophagic vacuoles (AVs) that accumulate in AD brains...
  52. pmc Guidelines for the use and interpretation of assays for monitoring autophagy in higher eukaryotes
    Daniel J Klionsky
    Life Sciences Institute, University of Michigan, Ann Arbor, Michigan 48109 2216, USA
    Autophagy 4:151-75. 2008
    ..In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to verify an autophagic response...
  53. doi Rapamycin inhibits polyglutamine aggregation independently of autophagy by reducing protein synthesis
    Matthew A King
    Southampton Neuroscience Group, School of Biological Sciences, University of Southampton Bassett Crescent East, Southampton SO16 7PX, UK
    Mol Pharmacol 73:1052-63. 2008
    ..This finding may have important therapeutic implications...
  54. ncbi Alfy, a novel FYVE-domain-containing protein associated with protein granules and autophagic membranes
    Anne Simonsen
    Department of Biochemistry, The Norwegian Radium Hospital, Montebello, Oslo 0310, Norway
    J Cell Sci 117:4239-51. 2004
    ..By electron microscopy, similar structures can be found within autophagosomes. We propose that Alfy might target cytosolic protein aggregates for autophagic degradation...
  55. ncbi The dynamics of autophagy visualized in live cells: from autophagosome formation to fusion with endo/lysosomes
    Edward T W Bampton
    Department of Biochemistry, University of Cambridge, Cambridge, UK
    Autophagy 1:23-36. 2005
    ..Use of fluorescent LC3 and a counter-fluorescent endosomal/lysosomal protein clearly allows the entire autophagic process to be followed by live cell imaging with high fidelity...
  56. pmc In vivo analysis of autophagy in response to nutrient starvation using transgenic mice expressing a fluorescent autophagosome marker
    Noboru Mizushima
    Department of Cell Biology, National Institute for Basic Biology, Okazaki 444 8585, Japan
    Mol Biol Cell 15:1101-11. 2004
    ..Our results suggest that the regulation of autophagy is organ dependent and the role of autophagy is not restricted to the starvation response. This transgenic mouse model is a useful tool to study mammalian autophagy...
  57. ncbi The role of autophagy during the early neonatal starvation period
    Akiko Kuma
    Time s Arrow and Biosignaling, PRESTO, Japan Science and Technology Agency, Kawaguchi 332 0012, Japan
    Nature 432:1032-6. 2004
    ..These results suggest that the production of amino acids by autophagic degradation of 'self' proteins, which allows for the maintenance of energy homeostasis, is important for survival during neonatal starvation...
  58. pmc Participation of autophagy in storage of lysosomes in neurons from mouse models of neuronal ceroid-lipofuscinoses (Batten disease)
    Masato Koike
    Department of Cell Biology and Neurosciences, Osaka University Graduate School of Medicine, Suita, Japan
    Am J Pathol 167:1713-28. 2005
    ..These data strongly argue for a major involvement of autophagy in the pathogenesis of Batten disease/lysosomal storage disorders...
  59. ncbi Coronavirus replication complex formation utilizes components of cellular autophagy
    Erik Prentice
    Department of Microbiology and Immunology, Elizabeth B Lamb Center for Pediatric Research, Vanderbilt University Medical Center, Nashville, Tennessee 37221, USA
    J Biol Chem 279:10136-41. 2004
    ..Furthermore, the rough endoplasmic reticulum is implicated as the possible source of membranes for replication complexes...
  60. ncbi Essential roles of Atg5 and FADD in autophagic cell death: dissection of autophagic cell death into vacuole formation and cell death
    Jong Ok Pyo
    Department of Life Science, Gwangju Institute of Science and Technology, Gwangju 500 712, Korea
    J Biol Chem 280:20722-9. 2005
    ..These results suggest that Atg5 plays a crucial role in IFN-gamma-induced autophagic cell death by interacting with FADD...
  61. ncbi Escape of intracellular Shigella from autophagy
    Michinaga Ogawa
    Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, 4 6 1, Shirokanedai, Minato ku, Tokyo 108 8639, Japan
    Science 307:727-31. 2005
    ..Rather, Shigella VirG, a protein required for intracellular actin-based motility, induced autophagy by binding to the autophagy protein, Atg5. In nonmutant Shigella, this binding is competitively inhibited by IcsB binding to VirG...
  62. ncbi Role of Bcl-2 family proteins in a non-apoptotic programmed cell death dependent on autophagy genes
    Shigeomi Shimizu
    Department of Post Genomics and Diseases, Osaka University Medical School, 2 2 Yamadaoka, Suita, Osaka 565 0871, Japan
    Nat Cell Biol 6:1221-8. 2004
    ..These results indicate that the Bcl-2 family of proteins not only regulates apoptosis, but also controls non-apoptotic programmed cell death that depends on the autophagy genes...
  63. ncbi The crystal structure of microtubule-associated protein light chain 3, a mammalian homologue of Saccharomyces cerevisiae Atg8
    Kenji Sugawara
    Department of Structural Biology, Graduate School of Pharmaceutical Sciences, Hokkaido University, Kita 12, Nishi 6, Kita ku, Sapporo 060 0812, Japan
    Genes Cells 9:611-8. 2004
    ..We also propose the functional implications of the ubiquitin fold as a recognition module of target proteins...
  64. ncbi Cellular autophagy machinery is not required for vaccinia virus replication and maturation
    Haiyan Zhang
    Department of Pharmacology, Cancer Institute of New Jersey, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, Piscataway, New Jersey 08854, USA
    Autophagy 2:91-5. 2006
    ..This study indicates that the cellular autophagy machinery is not required for the life-cycle of vaccinia virus, suggesting that the primary vaccinia viral membrane does not originate from the autophagic membrane...
  65. ncbi [Regulators of mammalian cellular autophagy]
    Taichi Hara
    Tanpakushitsu Kakusan Koso 51:1484-9. 2006
  66. ncbi [Molecular mechanism of autophagy: the role of the Apg12 conjugation system]
    Noboru Mizushima
    PRESTO, Japan Science and Technology Corporation JST, Department of Cell Biology, National Institute for Basic Biology, 38 Nishigonaka, Myodaijicho, Okazaki, Aichi 444 8585
    Seikagaku 74:523-37. 2002
  67. ncbi Autophagy-dependent viral recognition by plasmacytoid dendritic cells
    Heung Kyu Lee
    Department of Immunobiology, Yale University School of Medicine, New Haven, CT, USA
    Science 315:1398-401. 2007
    ..These results support a key role for autophagy in mediating ssRNA virus detection and interferon-alpha secretion by pDCs and suggest that cytosolic replication intermediates of viruses serve as pathogen signatures recognized by TLR7...
  68. ncbi LC3, GABARAP and GATE16 localize to autophagosomal membrane depending on form-II formation
    Yukiko Kabeya
    Department of Cell Biology, National Institute for Basic Biology, Myodaiji 38, Okazaki 444 8585, Japan
    J Cell Sci 117:2805-12. 2004
    ..Generation of the form II correlates with autophagosome association of GABARAP and GATE16. These results suggest that all mammalian Atg8 homologues receive a common modification to associate with autophagosomal membrane as the form II...
  69. ncbi [Methods for monitoring macroautophagy]
    Noboru Mizushima
    Tanpakushitsu Kakusan Koso 51:1542-8. 2006
  70. ncbi Mouse Apg10 as an Apg12-conjugating enzyme: analysis by the conjugation-mediated yeast two-hybrid method
    Noboru Mizushima
    PRESTO, Japan Science and Technology Corporation, 332 0012, Kawaguchi, Japan
    FEBS Lett 532:450-4. 2002
    ..This novel two-hybrid method, which we have named 'conjugation-mediated yeast two-hybrid', proves to be a simple and useful technique with which to analyze protein-protein conjugation...
  71. ncbi Autophagosome formation in mammalian cells
    Noboru Mizushima
    Department of Cell Biology, National Institute for Basic Biology, 38 Nishigonaka, Myodaiji, Okazaki 444 8585, Japan
    Cell Struct Funct 27:421-9. 2002
    ..These findings are now being applied to studies on the physiological roles of autophagy in mammals...
  72. ncbi SKD1 AAA ATPase-dependent endosomal transport is involved in autolysosome formation
    Atsuki Nara
    Department of Cell Biology, National Institute for Basic Biology, Myodaiji, Okazaki, Japan
    Cell Struct Funct 27:29-37. 2002
    ..These results indicate that SKD1-dependent endosomal membrane trafficking is required for formation of autolysosomes...
  73. ncbi Role of the Apg12 conjugation system in mammalian autophagy
    Noboru Mizushima
    PRESTO, Japan Science and Technology Corporation, 332 0012, Kawaguchi, Japan
    Int J Biochem Cell Biol 35:553-61. 2003
    ..Discovery of the Apg12 system has facilitated our understanding of the molecular mechanism of autophagosome formation...
  74. ncbi ALIS are stress-induced protein storage compartments for substrates of the proteasome and autophagy
    Jason Szeto
    Infection, Immunity, Injury and Repair Program, The Hospital for Sick Children, Toronto, Ontario, Canada
    Autophagy 2:189-99. 2006
    ..Together, these findings demonstrate that ALIS act as generalized stress-induced protein storage compartments for substrates of the proteasome and autophagy...
  75. ncbi Crystallization and preliminary X-ray analysis of LC3-I
    Kenji Sugawara
    Graduate School of Pharmaceutical Sciences, Hokkaido University, N 12, W 6, Kita ku, Sapporo 060 0812, Japan
    Acta Crystallogr D Biol Crystallogr 59:1464-5. 2003
    ..39, c = 36.89 A. The other form belongs to space group P4(1) or P4(3), with unit-cell parameters a = 60.48, c = 35.28 A. From the latter form, a complete diffraction data set was collected to 2.1 A resolution...
  76. ncbi Two ubiquitin-like conjugation systems essential for autophagy
    Yoshinori Ohsumi
    Department of Cell Biology, National Institute for Basic Biology, Myodaiji cho, Okazaki 444 8585, Japan
    Semin Cell Dev Biol 15:231-6. 2004
  77. ncbi Formation of the approximately 350-kDa Apg12-Apg5.Apg16 multimeric complex, mediated by Apg16 oligomerization, is essential for autophagy in yeast
    Akiko Kuma
    Department of Cell Biology, National Institute for Basic Biology, 38 Nishigonaka, Myodaiji, Okazaki 444 8585, Japan
    J Biol Chem 277:18619-25. 2002
    ..These results suggest that the Apg12-Apg5 conjugate and Apg16 form a multimeric complex mediated by the Apg16 homo-oligomer, and formation of the approximately 350-kDa complex is required for autophagy in yeast...
  78. ncbi Transcriptomic and proteomic analysis of a 14-3-3 gene-deficient yeast
    Tohru Ichimura
    Department of Chemistry, Graduate School of Science, Tokyo Metropolitan University, Hachioji shi, Tokyo 192 0397, Japan
    Biochemistry 43:6149-58. 2004
    ..This study presents the first comprehensive overview of the genes and proteins that are affected by the depletion of Bmh1/2p and extends the scope of knowledge of the regulatory roles of Bmh1/2p in S. cerevisiae...
  79. ncbi GFP-like proteins stably accumulate in lysosomes
    Hiroyuki Katayama
    Laboratory for Cell Function Dynamics, Advanced Technology Development Group, Brain Science Institute, RIKEN
    Cell Struct Funct 33:1-12. 2008
    ....
  80. pmc Promotion of tumorigenesis by heterozygous disruption of the beclin 1 autophagy gene
    Xueping Qu
    Department of Medicine, Columbia University College of Physicians and Surgeons, New York, New York 10032, USA
    J Clin Invest 112:1809-20. 2003
    ..Thus, mutation of beclin 1 or other autophagy genes may contribute to the pathogenesis of human cancers...
  81. ncbi Mouse Apg16L, a novel WD-repeat protein, targets to the autophagic isolation membrane with the Apg12-Apg5 conjugate
    Noboru Mizushima
    PRESTO, Japan Science and Technology Corporation, Kawaguchi 332 0012, Japan
    J Cell Sci 116:1679-88. 2003
    ..Because WD-repeat proteins provide a platform for protein-protein interactions, the approximately 800 kDa complex is expected to function in autophagosome formation, further interacting with other proteins in mammalian cells...
  82. ncbi Methods for monitoring autophagy
    Noboru Mizushima
    Department of Cell Biology, National Institute for Basic Biology, 38 Nishigonaka, Myodaiji, Okazaki 444 8585, Japan
    Int J Biochem Cell Biol 36:2491-502. 2004
    ..Importantly, most of these proteins are conserved in mammals. Using these probes, we can now specifically monitor autophagic activity...
  83. ncbi Intracellular inclusions containing mutant alpha1-antitrypsin Z are propagated in the absence of autophagic activity
    Takahiro Kamimoto
    Department of Cell Genetics, National Institute of Genetics, Mishima, Japan
    J Biol Chem 281:4467-76. 2006
    ....
  84. ncbi Collaboration of proteolytic systems
    Noboru Mizushima
    Autophagy 3:179-80. 2007
  85. pmc A critical role for the autophagy gene Atg5 in T cell survival and proliferation
    Heather H Pua
    Department of Immunology, Duke University Medical Center, Durham, NC 27710, USA
    J Exp Med 204:25-31. 2007
    ..These results demonstrate a critical role for Atg5 in multiple aspects of lymphocyte development and function and suggest that autophagy may be essential for both T lymphocyte survival and proliferation...
  86. pmc Constitutive activation of chaperone-mediated autophagy in cells with impaired macroautophagy
    Susmita Kaushik
    Departments of Anatomy and Structural Biology and Developmental and Molecular Biology, Marion Bessin Liver Research Center and Institute for Aging Research, Albert Einstein College of Medicine, Bronx, NY 10461, USA
    Mol Biol Cell 19:2179-92. 2008
    ..This work supports a direct cross-talk between these two forms of autophagy, and it identifies changes in the lysosomal compartment that underlie the basis for the communication between both autophagic pathways...
  87. ncbi The role of autophagy in cardiomyocytes in the basal state and in response to hemodynamic stress
    Atsuko Nakai
    Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine, 2 2 Yamadaoka, Suita Osaka 565 0871, Japan
    Nat Med 13:619-24. 2007
    ....
  88. ncbi [Physiological role in constitutive autophagy]
    Masaaki Komatsu
    Tanpakushitsu Kakusan Koso 51:1515-8. 2006
  89. pmc Involvement of autophagy in trypsinogen activation within the pancreatic acinar cells
    Daisuke Hashimoto
    Division of Developmental Genetics, Institute of Molecular Embryology and Genetics, Kumamoto University, Kumamoto 860 0811, Japan
    J Cell Biol 181:1065-72. 2008
    ..These results suggest that autophagy exerts devastating effects in pancreatic acinar cells by activation of trypsinogen to trypsin in the early stage of acute pancreatitis through delivering trypsinogen to the lysosome...
  90. ncbi Induction of autophagy in axonal dystrophy and degeneration
    Qing Jun Wang
    Laboratory of Mass Spectrometry and Gaseous Ion Chemistry, Rockefeller University, New York, New York 10021, USA
    J Neurosci 26:8057-68. 2006
    ..We propose that induction of autophagy serves as an early stress response in axonal dystrophy and may participate in the remodeling of axon structures...
  91. pmc Cerebral ischemia-hypoxia induces intravascular coagulation and autophagy
    Faisal Adhami
    Division of Developmental Biology, Cincinnati Children s Hospital Research Foundation, Room 3464, 3333 Burnet Ave, Cincinnati, OH 45229, USA
    Am J Pathol 169:566-83. 2006
    ..Together, these results suggest that ischemia-hypoxia is a powerful stimulus for spontaneous coagulation leading to reperfusion deficits and autophagic/lysosomal cell death in brain...
  92. ncbi Chemical inhibitor of nonapoptotic cell death with therapeutic potential for ischemic brain injury
    Alexei Degterev
    Department of Cell Biology, Harvard Medical School, 240 Longwood Avenue, Boston, Massachusetts 02115, USA
    Nat Chem Biol 1:112-9. 2005
    ..Our study identifies a previously undescribed basic cell-death pathway with potentially broad relevance to human pathologies...
  93. pmc Role of the UBL-UBA protein KPC2 in degradation of p27 at G1 phase of the cell cycle
    Taichi Hara
    Department of Molecular and Cellular Biology, Medical Institute of Bioregulation, Kyushu University, 3 1 1 Maidashi, Higashi ku, Fukuoka 812 8582, Japan
    Mol Cell Biol 25:9292-303. 2005
    ..These observations suggest that KPC2 cooperatively regulates p27 degradation with KPC1 and that the STI1 domain as well as the UBL and UBA domains of KPC2 are indispensable for its function...
  94. ncbi Structural basis for the specificity and catalysis of human Atg4B responsible for mammalian autophagy
    Kenji Sugawara
    Department of Structural Biology, Graduate School of Pharmaceutical Sciences, Hokkaido University, N 12, W 6, Kita ku, Sapporo 060 0812, Japan
    J Biol Chem 280:40058-65. 2005
    ..The structure and in vitro mutational analyses provide the basis for the specificity and catalysis of HsAtg4B. This will enable the design of Atg4-specific inhibitors that block autophagy...
  95. ncbi Bcl-2 antiapoptotic proteins inhibit Beclin 1-dependent autophagy
    Sophie Pattingre
    Department of Medicine, Columbia University College of Physicians and Surgeons, New York, New York 10032, USA
    Cell 122:927-39. 2005
    ..This antiautophagy function of Bcl-2 may help maintain autophagy at levels that are compatible with cell survival, rather than cell death...
  96. ncbi [Autophagy: a strategy for neogenesis]
    Noboru Mizushima
    Tanpakushitsu Kakusan Koso 50:393-402. 2005
  97. ncbi Autophagy defends cells against invading group A Streptococcus
    Ichiro Nakagawa
    Department of Oral and Molecular Microbiology, Osaka University Graduate School of Dentistry, 1 8 Yamadaoka, Suita Osaka 565 0871, Japan
    Science 306:1037-40. 2004
    ..In autophagy-deficient Atg5-/- cells, GAS survived, multiplied, and were released from the cells. Thus, the autophagic machinery can act as an innate defense system against invading pathogens...
  98. pmc Analysis of the role of autophagy in replication of herpes simplex virus in cell culture
    Diane E Alexander
    Department of Ophthalmology, Washington University School of Medicine, St Louis, MO 63110, USA
    J Virol 81:12128-34. 2007
    ..These data show that while ICP34.5 regulates autophagy, it is the prevention of translational arrest by ICP34.5 rather than its control of autophagy that is the pivotal determinant of efficient HSV-1 replication in primary cell culture...