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    Cell death and differentiation. 2014 Sep 19. pii: cdd2014137. doi: 10.1038/cdd.2014.137. pmc: PMC4262782
    Essential versus accessory aspects of cell death: recommendations of the NCCD 2015.
    Galluzzi L1,  Bravo-San Pedro JM2,  Vitale I3,  Aaronson SA4,  Abrams JM5,  Adam D6,  Alnemri ES7,  Altucci L8,  Andrews D9,  Annicchiarico-Petruzzelli M10,  Baehrecke EH11,  Bazan NG12,  Bertrand MJ13,  Bianchi K14,  Blagosklonny MV15,  Blomgren K16,  Borner C17,  Bredesen DE18,  Brenner C19,  Campanella M20,  Candi E21,  Cecconi F22,  Chan FK23,  Chandel NS24,  Cheng EH25,  Chipuk JE26,  Cidlowski JA27,  Ciechanover A28,  Dawson TM29,  Dawson VL30,  De Laurenzi V31,  De Maria R32,  Debatin KM33,  Di Daniele N34,  Dixit VM35,  Dynlacht BD36,  El-Deiry WS37,  Fimia GM38,  Flavell RA39,  Fulda S40,  Garrido C41,  Gougeon ML42,  Green DR43,  Gronemeyer H44,  Hajnoczky G45,  Hardwick JM46,  Hengartner MO47,  Ichijo H48,  Joseph B49,  Jost PJ50,  Kaufmann T51,  Kepp O52,  Klionsky DJ53,  Knight RA54,  Kumar S55,  Lemasters JJ56,  Levine B57,  Linkermann A58,  Lipton SA59,  Lockshin RA60,  López-Otín C61,  Lugli E62,  Madeo F63,  Malorni W64,  Marine JC65,  Martin SJ66,  Martinou JC67,  Medema JP68,  Meier P69,  Melino S70,  Mizushima N71,  Moll U72,  Muñoz-Pinedo C73,  Nuñez G74,  Oberst A75,  Panaretakis T76,  Penninger JM77,  Peter ME78,  Piacentini M79,  Pinton P80,  Prehn JH81,  Puthalakath H82,  Rabinovich GA83,  Ravichandran KS84,  Rizzuto R85,  Rodrigues CM86,  Rubinsztein DC87,  Rudel T88,  Shi Y89,  Simon HU90,  Stockwell BR91,  Szabadkai G92,  Tait SW93,  Tang HL94,  Tavernarakis N95,  Tsujimoto Y96,  Vanden Berghe T97,  Vandenabeele P98,  Villunger A99,  Wagner EF100,  Walczak H101,  White E102,  Wood WG103,  Yuan J104,  Zakeri Z105,  Zhivotovsky B106,  Melino G107,  Kroemer G108
    Author information
    11] Gustave Roussy Cancer Center, Villejuif, France [2] Equipe 11 labellisée par la Ligue Nationale contre le Cancer, Centre de Recherche des Cordeliers, Paris, France [3] Université Paris Descartes/Paris V, Sorbonne Paris Cité, Paris, France.
    21] Gustave Roussy Cancer Center, Villejuif, France [2] Equipe 11 labellisée par la Ligue Nationale contre le Cancer, Centre de Recherche des Cordeliers, Paris, France [3] INSERM, U1138, Gustave Roussy, Paris, France.
    3Regina Elena National Cancer Institute, Rome, Italy.
    4Department of Oncological Sciences, The Tisch Cancer Institute, Ichan School of Medicine at Mount Sinai, New York, NY, USA.
    5Department of Cell Biology, UT Southwestern Medical Center, Dallas, TX, USA.
    6Institute of Immunology, Christian-Albrechts University, Kiel, Germany.
    7Department of Biochemistry and Molecular Biology, Thomas Jefferson University, Philadelphia, PA, USA.
    8Dipartimento di Biochimica, Biofisica e Patologia Generale, Seconda Università degli Studi di Napoli, Napoli, Italy.
    9Department of Biochemistry and Medical Biophysics, University of Toronto, Toronto, ON, Canada.
    10Biochemistry Laboratory, Istituto Dermopatico dell'Immacolata - Istituto Ricovero Cura Carattere Scientifico (IDI-IRCCS), Rome, Italy.
    11Department of Cancer Biology, University of Massachusetts Medical School, Worcester, MA, USA.
    12Neuroscience Center of Excellence, School of Medicine, New Orleans, LA, USA.
    131] VIB Inflammation Research Center, Ghent, Belgium [2] Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium.
    141] Barts Cancer Institute, Cancer Research UK Centre of Excellence, London, UK [2] Queen Mary University of London, John Vane Science Centre, London, UK.
    15Department of Cell Stress Biology, Roswell Park Cancer Institute, Buffalo, NY, USA.
    16Karolinska University Hospital, Karolinska Institute, Stockholm, Sweden.
    17Institute of Molecular Medicine and Spemann Graduate School of Biology and Medicine, Albert-Ludwigs University, Freiburg, Germany.
    181] Buck Institute for Research on Aging, Novato, CA, USA [2] Department of Neurology, University of California, San Francisco (UCSF), San Francisco, CA, USA.
    191] INSERM, UMRS769, Châtenay Malabry, France [2] LabEx LERMIT, Châtenay Malabry, France [3] Université Paris Sud/Paris XI, Orsay, France.
    20Department of Comparative Biomedical Sciences and Consortium for Mitochondrial Research, University College London (UCL), London, UK.
    21Department of Experimental Medicine and Surgery, University of Rome Tor Vergata, Rome, Italy.
    221] Laboratory of Molecular Neuroembryology, IRCCS Fondazione Santa Lucia, Rome, Italy [2] Department of Biology, University of Rome Tor Vergata; Rome, Italy [3] Unit of Cell Stress and Survival, Danish Cancer Society Research Center, Copenhagen, Denmark.
    23Department of Pathology, University of Massachusetts Medical School, Worcester, MA, USA.
    24Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
    25Human Oncology and Pathogenesis Program and Department of Pathology, Memorial Sloan Kettering Cancer Center (MSKCC), New York, NY, USA.
    26Department of Oncological Sciences, The Tisch Cancer Institute, Ichan School of Medicine at Mount Sinai, New York, NY, USA.
    27Laboratory of Signal Transduction, National Institute of Environmental Health Sciences (NIEHS), National Institute of Health (NIH), North Carolina, NC, USA.
    28Tumor and Vascular Biology Research Center, The Rappaport Faculty of Medicine and Research Institute, Technion Israel Institute of Technology, Haifa, Israel.
    291] Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering (ICE), Departments of Neurology, Pharmacology and Molecular Sciences, Solomon H Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, USA [2] Adrienne Helis Malvin Medical Research Foundation, New Orleans, LA, USA.
    301] Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering (ICE), Departments of Neurology, Pharmacology and Molecular Sciences, Solomon H Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, USA [2] Adrienne Helis Malvin Medical Research Foundation, New Orleans, LA, USA.
    31Department of Experimental and Clinical Sciences, Gabriele d'Annunzio University, Chieti, Italy.
    32Regina Elena National Cancer Institute, Rome, Italy.
    33Department of Pediatrics and Adolescent Medicine, Ulm University Medical Center, Ulm, Germany.
    34Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy.
    35Department of Physiological Chemistry, Genentech, South San Francisco, CA, USA.
    36Department of Pathology and Cancer Institute, Smilow Research Center, New York University School of Medicine, New York, NY, USA.
    37Laboratory of Translational Oncology and Experimental Cancer Therapeutics, Department of Medicine (Hematology/Oncology), Penn State Hershey Cancer Institute, Penn State College of Medicine, Hershey, PA, USA.
    381] Department of Biological and Environmental Sciences and Technologies (DiSTeBA), University of Salento, Lecce, Italy [2] Department of Epidemiology and Preclinical Research, National Institute for Infectious Diseases Lazzaro Spallanzani, Istituto Ricovero Cura Carattere Scientifico (IRCCS), Rome, Italy.
    39Department of Immunobiology, Yale School of Medicine, New Haven, CT, USA.
    40Institute for Experimental Cancer Research in Pediatrics, Goethe University, Frankfurt, Germany.
    411] INSERM, U866, Dijon, France [2] Faculty of Medicine, University of Burgundy, Dijon, France.
    42Antiviral Immunity, Biotherapy and Vaccine Unit, Infection and Epidemiology Department, Institut Pasteur, Paris, France.
    43Department of Immunology, St Jude's Children's Research Hospital, Memphis, TN, USA.
    44Department of Functional Genomics and Cancer, Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Illkirch, France.
    45Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, Philadelphia, PA, USA.
    46W Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins University, Baltimore, MD, USA.
    47Institute of Molecular Life Sciences, University of Zurich, Zurich, Switzerland.
    48Laboratory of Cell Signaling, Graduate School of Pharmaceutical Sciences, University of Tokyo, Tokyo, Japan.
    49Department of Oncology-Pathology, Cancer Centrum Karolinska (CCK), Karolinska Institute, Stockholm, Sweden.
    50Medical Department for Hematology, Technical University of Munich, Munich, Germany.
    51Institute of Pharmacology, Medical Faculty, University of Bern, Bern, Switzerland.
    521] Equipe 11 labellisée par la Ligue Nationale contre le Cancer, Centre de Recherche des Cordeliers, Paris, France [2] INSERM, U1138, Gustave Roussy, Paris, France [3] Metabolomics and Cell Biology Platforms, Gustave Roussy Cancer Center, Villejuif, France.
    53Life Sciences Institute, University of Michigan, Ann Arbor, MI, USA.
    541] Medical Molecular Biology Unit, Institute of Child Health, University College London (UCL), London, UK [2] Medical Research Council Toxicology Unit, Leicester, UK.
    551] Centre for Cancer Biology, University of South Australia, Adelaide, SA, Australia [2] School of Medicine and School of Molecular and Biomedical Science, University of Adelaide, Adelaide, SA, Australia.
    56Departments of Drug Discovery and Biomedical Sciences and Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston, SC, USA.
    571] Center for Autophagy Research, University of Texas, Southwestern Medical Center, Dallas, TX, USA [2] Howard Hughes Medical Institute (HHMI), Chevy Chase, MD, USA.
    58Division of Nephrology and Hypertension, Christian-Albrechts University, Kiel, Germany.
    591] The Scripps Research Institute, La Jolla, CA, USA [2] Sanford-Burnham Center for Neuroscience, Aging, and Stem Cell Research, La Jolla, CA, USA [3] Salk Institute for Biological Studies, La Jolla, CA, USA [4] University of California, San Diego (UCSD), San Diego, CA, USA.
    60Department of Biological Sciences, St. John's University, Queens, NY, USA.
    61Department of Biochemistry and Molecular Biology, Faculty of Medecine, Instituto Universitario de Oncología (IUOPA), University of Oviedo, Oviedo, Spain.
    62Unit of Clinical and Experimental Immunology, Humanitas Clinical and Research Center, Milan, Italy.
    63Institute of Molecular Biosciences, University of Graz, Graz, Austria.
    641] Department of Therapeutic Research and Medicine Evaluation, Istituto Superiore di Sanita (ISS), Roma, Italy [2] San Raffaele Institute, Sulmona, Italy.
    651] Laboratory for Molecular Cancer Biology, Center for the Biology of Disease, Leuven, Belgium [2] Laboratory for Molecular Cancer Biology, Center of Human Genetics, Leuven, Belgium.
    66Department of Genetics, The Smurfit Institute, Trinity College, Dublin, Ireland.
    67Department of Cell Biology, University of Geneva, Geneva, Switzerland.
    68Laboratory for Experiments Oncology and Radiobiology (LEXOR), Academic Medical Center (AMC), Amsterdam, The Netherlands.
    69Institute of Cancer Research, The Breakthrough Toby Robins Breast Cancer Research Centre, London, UK.
    70Department of Chemical Sciences and Technologies, University of Rome Tor Vergata, Rome, Italy.
    71Graduate School and Faculty of Medicine, University of Tokyo, Tokyo, Japan.
    72Department of Pathology, Stony Brook University, Stony Brook, NY, USA.
    73Cell Death Regulation Group, Bellvitge Biomedical Research Institute (IDIBELL), Barcelona, Spain.
    74Department of Pathology and Comprehensive Cancer Center, University of Michigan Medical School, Ann Arbor, MI, USA.
    75Department of Immunology, University of Washington, Seattle, WA, USA.
    76Department of Oncology-Pathology, Cancer Centrum Karolinska (CCK), Karolinska Institute, Stockholm, Sweden.
    77Institute of Molecular Biotechnology of the Austrian Academy of Sciences, Vienna, Austria.
    78Department of Hematology/Oncology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
    791] Department of Biology, University of Rome Tor Vergata; Rome, Italy [2] Department of Epidemiology and Preclinical Research, National Institute for Infectious Diseases Lazzaro Spallanzani, Istituto Ricovero Cura Carattere Scientifico (IRCCS), Rome, Italy.
    80Department of Morphology, Surgery and Experimental Medicine, Section of Pathology, Oncology and Experimental Biology and LTTA Center, University of Ferrara, Ferrara, Italy.
    81Department of Physiology and Medical Physics, Royal College of Surgeons, Dublin, Ireland.
    82Department of Biochemistry, La Trobe Institute of Molecular Science, La Trobe University, Melbourne, Australia.
    83Laboratory of Immunopathology, Instituto de Biología y Medicina Experimental (IBYME), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires, Argentina.
    84Department of Microbiology, Immunology and Cancer Biology, University of Virginia, Charlottesville, VA, USA.
    85Department Biomedical Sciences, University of Padova, Padova, Italy.
    86Research Institute for Medicines, Faculty of Pharmacy, University of Lisbon, Lisbon, Portugal.
    87Department of Medical Genetics, Cambridge Institute for Medical Research, University of Cambridge School of Clinical Medicine, Cambridge, UK.
    88Department of Microbiology, University of Würzburg; Würzburg, Germany.
    89Soochow Institute for Translational Medicine, Soochow University, Suzhou, China.
    90Institute of Pharmacology, University of Bern, Bern, Switzerland.
    911] Howard Hughes Medical Institute (HHMI), Chevy Chase, MD, USA [2] Departments of Biological Sciences and Chemistry, Columbia University, New York, NY, USA.
    921] Department Biomedical Sciences, University of Padova, Padova, Italy [2] Department of Cell and Developmental Biology and Consortium for Mitochondrial Research, University College London (UCL), London, UK.
    931] Cancer Research UK Beatson Institute, Glasgow, UK [2] Institute of Cancer Sciences, University of Glasgow, Glasgow, UK.
    94W Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins University, Baltimore, MD, USA.
    951] Institute of Molecular Biology and Biotechnology, Foundation for Research and Technology-Hellas, Heraklion, Crete, Greece [2] Department of Basic Sciences, Faculty of Medicine, University of Crete, Heraklion, Crete, Greece.
    96Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan.
    971] VIB Inflammation Research Center, Ghent, Belgium [2] Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium.
    981] VIB Inflammation Research Center, Ghent, Belgium [2] Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium [3] Methusalem Program, Ghent University, Ghent, Belgium.
    99Division of Developmental Immunology, Biocenter, Medical University Innsbruck, Innsbruck, Austria.
    100Cancer Cell Biology Program, Spanish National Cancer Research Centre (CNIO), Madrid, Spain.
    101Centre for Cell Death, Cancer and Inflammation (CCCI), UCL Cancer Institute, University College London (UCL), London, UK.
    102Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, USA.
    1031] Department of Pharmacology, University of Minnesota School of Medicine, Minneapolis, MN, USA [2] Geriatric Research, Education and Clinical Center, VA Medical Center, Minneapolis, MN, USA.
    104Department of Cell Biology, Harvard Medical School, Boston, MA, USA.
    1051] Department of Biology, Queens College, Queens, NY, USA [2] Graduate Center, City University of New York (CUNY), Queens, NY, USA.
    1061] Division of Toxicology, Institute of Environmental Medicine, Karolinska Institute, Stockholm, Sweden [2] Faculty of Fundamental Medicine, Lomonosov Moscow State University, Moscow, Russia.
    1071] Department of Experimental Medicine and Surgery, University of Rome Tor Vergata, Rome, Italy [2] Medical Research Council Toxicology Unit, Leicester, UK.
    1081] Equipe 11 labellisée par la Ligue Nationale contre le Cancer, Centre de Recherche des Cordeliers, Paris, France [2] Université Paris Descartes/Paris V, Sorbonne Paris Cité, Paris, France [3] INSERM, U1138, Gustave Roussy, Paris, France [4] Metabolomics and Cell Biology Platforms, Gustave Roussy Cancer Center, Villejuif, France [5] Pôle de Biologie, Hôpital Européen Georges Pompidou, AP-HP, Paris, France.
    Abstract

    Cells exposed to extreme physicochemical or mechanical stimuli die in an uncontrollable manner, as a result of their immediate structural breakdown. Such an unavoidable variant of cellular demise is generally referred to as 'accidental cell death' (ACD). In most settings, however, cell death is initiated by a genetically encoded apparatus, correlating with the fact that its course can be altered by pharmacologic or genetic interventions. 'Regulated cell death' (RCD) can occur as part of physiologic programs or can be activated once adaptive responses to perturbations of the extracellular or intracellular microenvironment fail. The biochemical phenomena that accompany RCD may be harnessed to classify it into a few subtypes, which often (but not always) exhibit stereotyped morphologic features. Nonetheless, efficiently inhibiting the processes that are commonly thought to cause RCD, such as the activation of executioner caspases in the course of apoptosis, does not exert true cytoprotective effects in the mammalian system, but simply alters the kinetics of cellular demise as it shifts its morphologic and biochemical correlates. Conversely, bona fide cytoprotection can be achieved by inhibiting the transduction of lethal signals in the early phases of the process, when adaptive responses are still operational. Thus, the mechanisms that truly execute RCD may be less understood, less inhibitable and perhaps more homogeneous than previously thought. Here, the Nomenclature Committee on Cell Death formulates a set of recommendations to help scientists and researchers to discriminate between essential and accessory aspects of cell death.


    Publikations ID: 25236395
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