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Guidelines for the use and interpretation of assays for monitoring cell death in higher eukaryotes

Authors
  • Galluzzi, L1, 2, 3
  • Aaronson, SA4
  • Abrams, J5
  • Alnemri, ES6
  • Andrews, DW7
  • Baehrecke, EH8
  • Bazan, NG9
  • Blagosklonny, MV10
  • Blomgren, K11, 12
  • Borner, C13
  • Bredesen, DE14, 15
  • Brenner, C16, 17
  • Castedo, M1, 2, 3
  • Cidlowski, JA18
  • Ciechanover, A19
  • Cohen, GM20
  • De Laurenzi, V21
  • De Maria, R22, 23
  • Deshmukh, M24
  • Dynlacht, BD25
  • And 59 more
  • 1 INSERM, U848, F-94805 Villejuif, France
  • 2 Institut Gustave Roussy, F-94805 Villejuif, France
  • 3 Université Paris Sud-XI, F-94805 Villejuif, France
  • 4 Department of Oncological Sciences, Mount Sinai School of Medicine, New York, NY 10029, USA
  • 5 Department of Cell Biology, UT Southwestern Medical Center, Dallas, TX 75390, USA
  • 6 Department of Biochemistry and Molecular Biology, Center for Apoptosis Research, Kimmel Cancer Institute, Thomas Jefferson University, Philadelphia, PA 19107-5587, USA
  • 7 Department of Biochemistry and Biomedical Sciences, McMaster University, L8N 3Z5 Hamilton, Canada
  • 8 Department of Cancer Biology, University of Massachusetts Medical School, Worcester, MA 01605-2324, USA
  • 9 Neuroscience Center of Excellence, School of Medicine, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA
  • 10 Roswell Park Cancer Institute, Buffalo, NY 14263, USA
  • 11 Center for Brain Repair and Rehabilitation, Institute of Neuroscience and Physiology, University of Gothenburg, SE-405 30 Gothenburg, Sweden
  • 12 Department of Pediatric Oncology, The Queen Silvia Children’s Hospital, SE-416 85 Gothenburg, Sweden
  • 13 Institute of Molecular Medicine and Cell Research (ZBMZ), Albert-Ludwigs-Universität Freiburg, 79104 Freiburg, Germany
  • 14 Buck Institute for Age Research, Novato, CA 94945, USA
  • 15 University of California – San Francisco, San Francisco, CA 94143, USA
  • 16 University of Versailles/St Quentin, 78035 Versailles, France
  • 17 CNRS, UMR8159, 78035 Versailles, France
  • 18 National Institutes of Environmental Health Sciences, NIH, Duhram, NC 27709, USA
  • 19 Vascular and Tumor Biology Research Center, The Rappaport Faculty of Medicine, Technion – Israel Institute of Technology, 31096 Haifa, Israel
  • 20 Medical Research Council, Toxicology Unit, Leicester University, Leicester LE1 9HN, UK
  • 21 Dipartimento di Scienze Biomediche, Università ‘G. d’Annunzio’ Chieti-Pescara, 66100 Chieti, Italy
  • 22 Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, 00161 Rome, Italy
  • 23 Mediterranean Institute of Oncology, 95030 Catania, Italy
  • 24 Neuroscience Center, Department of Cell and Developmental Biology, University of North Carolina, Chapel Hill, NC 27599-7250, USA
  • 25 Department of Pathology, New York University School of Medicine, New York, NY 10016, USA
  • 26 Hematology-Oncology Division, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
  • 27 Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA
  • 28 Howard Hughes Medical Institute, Chevy Chase, MD 20815-6789, USA
  • 29 University Children’s Hospital, 89075 Ulm, Germany
  • 30 INSERM, UMR866, 21049 Dijon, France
  • 31 Faculty of Medicine and Pharmacy, University of Burgundy, 21049 Dijon, France
  • 32 INSERM, U631, 13288 Marseille, France
  • 33 CNRS, UMR6102, 13288 Marseille, France
  • 34 Centre d’Immunologie de Marseille-Luminy, Aix Marseille Université, 13288 Marseille, France
  • 35 Institut Pasteur, Antiviral Immunity, Biotherapy and Vaccine Unit, 75015 Paris, France
  • 36 Department of Immunology, St. Jude Children′s Research Hospital, Memphis, TN 38105, USA
  • 37 Department of Cancer Biology – Institut de Génétique et de Biologie Moléculaire et Cellulaire, 67404 Illkirch, France
  • 38 CNRS, UMR7104, 67404 Illkirch, France
  • 39 INSERM, U964, 67404 Illkirch, France;
  • 40 Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, Philadelphia, PA 19107, USA
  • 41 Department of Pharmacology and Molecular Sciences, Johns Hopkins University, Baltimore, MD 21205, USA
  • 42 Institute of Molecular Biology, University of Zurich, 8057 Zurich, Switzerland
  • 43 Graduate School of Pharmaceutical Sciences, University of Tokyo, Tokyo 113-0033, Japan
  • 44 Danish Cancer Society, Department of Apoptosis, Institute of Cancer Biology, DK-2100 Copenhagen, Denmark
  • 45 Department of Molecular Genetics, Weizmann Institute of Science, 76100 Rehovot, Israel
  • 46 Life Sciences Institute and Department of Molecular, Cellular, and Developmental Biology and Biological Chemistry, University of Michigan, Ann Arbor, MI 48109, USA
  • 47 Institute of Child Health, University College London, London WC1N 1EH, UK
  • 48 Duke University School of Medicine, Durham, NC 27710, USA
  • 49 Centre for Cancer Biology, Hanson Institute, Adelaide, South Australia 5000, Australia
  • 50 Southwestern Medical Center, University of Texas, Dallas, TX 75390, USA
  • 51 Burnham Institute for Medical Research, La Jolla, CA 92037, USA
  • 52 The Salk Institute for Biological Studies, La Jolla, CA 92037, USA
  • 53 The Scripps Research Institute, La Jolla, CA 92037, USA
  • 54 Univerisity of California-San Diego, La Jolla, CA 92093, USA
  • 55 Immunotechnology Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA
  • 56 Institute of Molecular Biosciences, University of Graz, 8010 Graz, Austria
  • 57 Department of Therapeutic Research and Medicines Evaluation, Section of Cell Aging and Degeneration, Istituto Superiore di Sanità, 00161 Rome, Italy
  • 58 Laboratory for Molecular Cancer Biology, VIB, 9052 Ghent, Belgium
  • 59 Department for Molecular Biology, Ghent University, 9052 Ghent, Belgium
  • 60 Department of Genetics, Trinity College, Dublin 2, Ireland
  • 61 Center for Experimental and Molecular Medicine, Academic Medical Center, 1105 AZ Amsterdam, The Netherlands
  • 62 University of Amsterdam, 1012 ZA Amsterdam, The Netherlands
  • 63 Apoptosis, Cancer, and Development Laboratory, Centre Léon Berard, 69008 Lyon, France
  • 64 CNRS, UMR5238, 69008 Lyon, France
  • 65 Université de Lyon, 69008 Lyon, France
  • 66 Department of Experimental Medicine and Biochemical Sciences, University of Rome ‘Tor Vergata’, 00133 Rome, Italy
  • 67 Department of Pathology, Stony Brook University, Stony Brook, NY 11794-8691, USA
  • 68 Department of Molecular Oncology, Goöttingen Center of Molecular Biosciences, 37077 Göttingen, Germany
  • 69 Faculty of Medicine, University of Göttingen, 37077 Göttingen, Germany
  • 70 Department of Medical Chemistry, Graduate School of Medicine, University of Kyoto, Kyoto 606-8501, Japan
  • 71 Merck Research Laboratories, Rahway, NJ 07065-0900, USA
  • 72 University of Michigan Medical School, Ann Arbor, MI 48109, USA
  • 73 Department of Molecular Cell Biology, Weizmann Institute of Science, 76100 Rehovot, Israel
  • 74 Institute of Molecular Biotechnology of the Austrian Academy of Science, 1030 Vienna, Austria
  • 75 Department of Physiology, Yong Loo Lin School of Medicine, Graduate School for Integrative Sciences and Engineering, National University of Singapore, 117597 Singapore
  • 76 Singapore-MIT Alliance, National University of Singapore, 117576 Singapore
  • 77 Duke-NUS Graduate Medical School, 169547 Singapore
  • 78 Ben May Department for Cancer Research, University of Chicago, Chicago, IL 60637, USA
  • 79 Laboratory of Cell Biology, National Institute for Infectious Diseases IRCCS ‘L. Spallanzani’, 00149 Rome, Italy
  • 80 Department of Biology, University of Rome ‘Tor Vergata’, 00133 Rome, Italy
  • 81 Department of Physiology and Medical Physics, Royal College of Surgeons in Ireland, Dublin 2, Ireland
  • 82 Department of Biochemistry, La Trobe University, 3086 Victoria, Australia
  • 83 Laboratorio de Inmunopatología, Instituto de Biología y Medicina Experimental (IBYME- CONICET), C1428 Buenos Aires, Argentina
  • 84 Department of Biomedical Sciences, University of Padova, 35121 Padova, Italy
  • 85 iMed.UL, Faculty of Pharmacy, University of Lisbon, 1649-003 Lisbon, Portugal
  • 86 Cambridge Institute for Medical Research, Cambridge CB2 0XY, UK
  • 87 Biocenter, University of Würzburg, 97074 Würzburg, Germany
  • 88 Department of Cell Physiology and Metabolism, University of Geneva Medical School, 1211 Geneva, Switzerland
  • 89 Dulbecco-Telethon Institute, Venetian Institute of Molecular Medicine, 35129 Padova, Italy
  • 90 Department of Pharmacology, University of Bern, 3010 Bern, Switzerland
  • 91 Laboratory of Apoptosis and Cancer Biology, The Rockefeller University, New York, NY 10065, USA
  • 92 Department of Biochemistry, University of Lausanne, 1066 Epalinges, Switzerland
  • 93 Department of Medical Genetics, Osaka University Medical School, Osaka 565-0871, Japan
  • 94 Department for Molecular Biomedical Research, VIB, 9052 Ghent, Belgium
  • 95 The Beatson Institute for Cancer Research, Glasgow G61 1BD, UK
  • 96 Neurological Disorders and Stroke, NIH, Bethesda, MD 20892, USA
  • 97 Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA
  • 98 Institute of Environmental Medicine, Division of Toxicology, Karolinska Institute, SE- 171 77 Stockholm, Sweden
Type
Published Article
Journal
Cell death and differentiation
Publication Date
Apr 17, 2009
Volume
16
Issue
8
Pages
1093–1107
Identifiers
DOI: 10.1038/cdd.2009.44
PMID: 19373242
PMCID: PMC2757140
Source
PubMed Central
Keywords
License
Unknown

Abstract

Cell death is essential for a plethora of physiological processes, and its deregulation characterizes numerous human diseases. Thus, the in-depth investigation of cell death and its mechanisms constitutes a formidable challenge for fundamental and applied biomedical research, and has tremendous implications for the development of novel therapeutic strategies. It is, therefore, of utmost importance to standardize the experimental procedures that identify dying and dead cells in cell cultures and/or in tissues, from model organisms and/or humans, in healthy and/or pathological scenarios. Thus far, dozens of methods have been proposed to quantify cell death-related parameters. However, no guidelines exist regarding their use and interpretation, and nobody has thoroughly annotated the experimental settings for which each of these techniques is most appropriate. Here, we provide a nonexhaustive comparison of methods to detect cell death with apoptotic or nonapoptotic morphologies, their advantages and pitfalls. These guidelines are intended for investigators who study cell death, as well as for reviewers who need to constructively critique scientific reports that deal with cellular demise. Given the difficulties in determining the exact number of cells that have passed the point-of-no-return of the signaling cascades leading to cell death, we emphasize the importance of performing multiple, methodologically unrelated assays to quantify dying and dead cells.

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