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Klionsky DJ, Petroni G, Amaravadi RK, et al. Autophagy in major human diseases. EMBO J. 2021;40(19):e108863doi: 10.15252/embj.2021108863.
Klionsky, D. J., Petroni, G., Amaravadi, R. K., Baehrecke, E. H., Ballabio, A., Boya, P., Bravo-San Pedro, J. M., Cadwell, K., Cecconi, F., Choi, A. M. K., Choi, M. E., Chu, C. T., Codogno, P., Colombo, M. I., Cuervo, A. M., Deretic, V., Dikic, I., Elazar, Z., Eskelinen, E. L., Fimia, G. M., Gewirtz, D. A., Green, D. R., Hansen, M., Jäättelä, M., Johansen, T., Juhász, G., Karantza, V., Kraft, C., Kroemer, G., Ktistakis, N. T., Kumar, S., Lopez-Otin, C., Macleod, K. F., Madeo, F., Martinez, J., Meléndez, A., Mizushima, N., Münz, C., Penninger, J. M., Perera, R. M., Piacentini, M., Reggiori, F., Rubinsztein, D. C., Ryan, K. M., Sadoshima, J., Santambrogio, L., Scorrano, L., Simon, H. U., Simon, A. K., Simonsen, A., Stolz, A., Tavernarakis, N., Tooze, S. A., Yoshimori, T., Yuan, J., Yue, Z., Zhong, Q., Galluzzi, L., & Pietrocola, F. (2021). Autophagy in major human diseases. The EMBO journal, 40(19), e108863. https://doi.org/10.15252/embj.2021108863
Klionsky, Daniel J, et al. "Autophagy in major human diseases." The EMBO journal vol. 40,19 (2021): e108863. doi: https://doi.org/10.15252/embj.2021108863
Klionsky DJ, Petroni G, Amaravadi RK, Baehrecke EH, Ballabio A, Boya P, Bravo-San Pedro JM, Cadwell K, Cecconi F, Choi AMK, Choi ME, Chu CT, Codogno P, Colombo MI, Cuervo AM, Deretic V, Dikic I, Elazar Z, Eskelinen EL, Fimia GM, Gewirtz DA, Green DR, Hansen M, Jäättelä M, Johansen T, Juhász G, Karantza V, Kraft C, Kroemer G, Ktistakis NT, Kumar S, Lopez-Otin C, Macleod KF, Madeo F, Martinez J, Meléndez A, Mizushima N, Münz C, Penninger JM, Perera RM, Piacentini M, Reggiori F, Rubinsztein DC, Ryan KM, Sadoshima J, Santambrogio L, Scorrano L, Simon HU, Simon AK, Simonsen A, Stolz A, Tavernarakis N, Tooze SA, Yoshimori T, Yuan J, Yue Z, Zhong Q, Galluzzi L, Pietrocola F. Autophagy in major human diseases. EMBO J. 2021 Oct 01;40(19):e108863. doi: 10.15252/embj.2021108863. Epub 2021 Aug 30. PMID: 34459017; PMCID: PMC8488577.
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EMBO J. 2021 Oct 01;40(19):e108863. doi: 10.15252/embj.2021108863. Epub 2021 Aug 30.

Autophagy in major human diseases.

The EMBO journal

Daniel J Klionsky, Giulia Petroni, Ravi K Amaravadi, Eric H Baehrecke, Andrea Ballabio, Patricia Boya, José Manuel Bravo-San Pedro, Ken Cadwell, Francesco Cecconi, Augustine M K Choi, Mary E Choi, Charleen T Chu, Patrice Codogno, Maria Isabel Colombo, Ana Maria Cuervo, Vojo Deretic, Ivan Dikic, Zvulun Elazar, Eeva-Liisa Eskelinen, Gian Maria Fimia, David A Gewirtz, Douglas R Green, Malene Hansen, Marja Jäättelä, Terje Johansen, Gábor Juhász, Vassiliki Karantza, Claudine Kraft, Guido Kroemer, Nicholas T Ktistakis, Sharad Kumar, Carlos Lopez-Otin, Kay F Macleod, Frank Madeo, Jennifer Martinez, Alicia Meléndez, Noboru Mizushima, Christian Münz, Josef M Penninger, Rushika M Perera, Mauro Piacentini, Fulvio Reggiori, David C Rubinsztein, Kevin M Ryan, Junichi Sadoshima, Laura Santambrogio, Luca Scorrano, Hans-Uwe Simon, Anna Katharina Simon, Anne Simonsen, Alexandra Stolz, Nektarios Tavernarakis, Sharon A Tooze, Tamotsu Yoshimori, Junying Yuan, Zhenyu Yue, Qing Zhong, Lorenzo Galluzzi, Federico Pietrocola

Affiliations

  1. Life Sciences Institute, University of Michigan, Ann Arbor, MI, USA.
  2. Department of Radiation Oncology, Weill Cornell Medical College, New York, NY, USA.
  3. Department of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
  4. Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, USA.
  5. Department of Molecular, Cell and Cancer Biology, University of Massachusetts Medical School, Worcester, MA, USA.
  6. Telethon Institute of Genetics and Medicine, Pozzuoli, Italy.
  7. Department of Translational Medical Sciences, Section of Pediatrics, Federico II University, Naples, Italy.
  8. Department of Molecular and Human Genetics, Baylor College of Medicine, and Jan and Dan Duncan Neurological Research Institute, Texas Children Hospital, Houston, TX, USA.
  9. Margarita Salas Center for Biological Research, Spanish National Research Council, Madrid, Spain.
  10. Faculty of Medicine, Department Section of Physiology, Complutense University of Madrid, Madrid, Spain.
  11. Center for Networked Biomedical Research in Neurodegenerative Diseases (CIBERNED), Madrid, Spain.
  12. Kimmel Center for Biology and Medicine at the Skirball Institute, New York University Grossman School of Medicine, New York, NY, USA.
  13. Department of Microbiology, New York University Grossman School of Medicine, New York, NY, USA.
  14. Division of Gastroenterology and Hepatology, Department of Medicine, New York University Langone Health, New York, NY, USA.
  15. Cell Stress and Survival Unit, Center for Autophagy, Recycling and Disease (CARD), Danish Cancer Society Research Center, Copenhagen, Denmark.
  16. Department of Pediatric Onco-Hematology and Cell and Gene Therapy, IRCCS Bambino Gesù Children's Hospital, Rome, Italy.
  17. Department of Biology, University of Rome 'Tor Vergata', Rome, Italy.
  18. Division of Pulmonary and Critical Care Medicine, Joan and Sanford I. Weill Department of Medicine, Weill Cornell Medicine, New York, NY, USA.
  19. New York-Presbyterian Hospital, Weill Cornell Medicine, New York, NY, USA.
  20. Division of Nephrology and Hypertension, Joan and Sanford I. Weill Department of Medicine, Weill Cornell Medicine, New York, NY, USA.
  21. Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
  22. Institut Necker-Enfants Malades, INSERM U1151-CNRS UMR 8253, Paris, France.
  23. Université de Paris, Paris, France.
  24. Laboratorio de Mecanismos Moleculares Implicados en el Tráfico Vesicular y la Autofagia-Instituto de Histología y Embriología (IHEM)-Universidad Nacional de Cuyo, CONICET- Facultad de Ciencias Médicas, Mendoza, Argentina.
  25. Department of Developmental and Molecular Biology, Albert Einstein College of Medicine, Bronx, NY, USA.
  26. Institute for Aging Studies, Albert Einstein College of Medicine, Bronx, NY, USA.
  27. Autophagy Inflammation and Metabolism (AIM, Center of Biomedical Research Excellence, University of New Mexico Health Sciences Center, Albuquerque, NM, USA.
  28. Department of Molecular Genetics and Microbiology, University of New Mexico Health Sciences Center, Albuquerque, NM, USA.
  29. Institute of Biochemistry II, School of Medicine, Goethe University, Frankfurt, Frankfurt am Main, Germany.
  30. Buchmann Institute for Molecular Life Sciences, Goethe University, Frankfurt, Frankfurt am Main, Germany.
  31. Department of Biomolecular Sciences, The Weizmann Institute of Science, Rehovot, Israel.
  32. Institute of Biomedicine, University of Turku, Turku, Finland.
  33. Department of Molecular Medicine, Sapienza University of Rome, Rome, Italy.
  34. Department of Epidemiology, Preclinical Research, and Advanced Diagnostics, National Institute for Infectious Diseases 'L. Spallanzani' IRCCS, Rome, Italy.
  35. Department of Pharmacology and Toxicology, School of Medicine, Virginia Commonwealth University, Richmond, VA, USA.
  36. Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN, USA.
  37. Sanford Burnham Prebys Medical Discovery Institute, Program of Development, Aging, and Regeneration, La Jolla, CA, USA.
  38. Cell Death and Metabolism, Center for Autophagy, Recycling & Disease, Danish Cancer Society Research Center, Copenhagen, Denmark.
  39. Department of Cellular and Molecular Medicine, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark.
  40. Department of Medical Biology, Molecular Cancer Research Group, University of Tromsø-The Arctic University of Norway, Tromsø, Norway.
  41. Institute of Genetics, Biological Research Center, Szeged, Hungary.
  42. Department of Anatomy, Cell and Developmental Biology, Eötvös Loránd University, Budapest, Hungary.
  43. Merck & Co., Inc., Kenilworth, NJ, USA.
  44. Institute of Biochemistry and Molecular Biology, ZBMZ, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
  45. CIBSS - Centre for Integrative Biological Signalling Studies, University of Freiburg, Freiburg, Germany.
  46. Centre de Recherche des Cordeliers, Equipe Labellisée par la Ligue Contre le Cancer, Université de Paris, Sorbonne Université, Inserm U1138, Institut Universitaire de France, Paris, France.
  47. Metabolomics and Cell Biology Platforms, Institut Gustave Roussy, Villejuif, France.
  48. Pôle de Biologie, Hôpital Européen Georges Pompidou, AP-HP, Paris, France.
  49. Suzhou Institute for Systems Medicine, Chinese Academy of Medical Sciences, Suzhou, China.
  50. Karolinska Institute, Department of Women's and Children's Health, Karolinska University Hospital, Stockholm, Sweden.
  51. Signalling Programme, Babraham Institute, Cambridge, UK.
  52. Centre for Cancer Biology, University of South Australia, Adelaide, SA, Australia.
  53. Faculty of Health and Medical Sciences, University of Adelaide, Adelaide, SA, Australia.
  54. Departamento de Bioquímica y Biología Molecular, Facultad de Medicina, Instituto Universitario de Oncología del Principado de Asturias (IUOPA), Universidad de Oviedo, Oviedo, Spain.
  55. Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Madrid, Spain.
  56. The Ben May Department for Cancer Research, The Gordon Center for Integrative Sciences, W-338, The University of Chicago, Chicago, IL, USA.
  57. The University of Chicago, Chicago, IL, USA.
  58. Institute of Molecular Biosciences, NAWI Graz, University of Graz, Graz, Austria.
  59. BioTechMed-Graz, Graz, Austria.
  60. Field of Excellence BioHealth - University of Graz, Graz, Austria.
  61. Immunity, Inflammation and Disease Laboratory, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, NC, USA.
  62. Biology Department, Queens College, City University of New York, Flushing, NY, USA.
  63. The Graduate Center Biology and Biochemistry PhD Programs of the City University of New York, New York, NY, USA.
  64. Department of Biochemistry and Molecular Biology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
  65. Viral Immunobiology, Institute of Experimental Immunology, University of Zurich, Zurich, Switzerland.
  66. Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), Vienna BioCenter (VBC), Vienna, Austria.
  67. Department of Medical Genetics, Life Sciences Institute, University of British Columbia, Vancouver, BC, Canada.
  68. Department of Anatomy, University of California, San Francisco, San Francisco, CA, USA.
  69. Department of Pathology, University of California, San Francisco, San Francisco, CA, USA.
  70. Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA, USA.
  71. Department of Biology, University of Rome "Tor Vergata", Rome, Italy.
  72. Laboratory of Molecular Medicine, Institute of Cytology Russian Academy of Science, Saint Petersburg, Russia.
  73. Department of Biomedical Sciences of Cells & Systems, Molecular Cell Biology Section, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
  74. Department of Medical Genetics, Cambridge Institute for Medical Research, University of Cambridge, Cambridge, UK.
  75. UK Dementia Research Institute, University of Cambridge, Cambridge, UK.
  76. Cancer Research UK Beatson Institute, Glasgow, UK.
  77. Institute of Cancer Sciences, University of Glasgow, Glasgow, UK.
  78. Department of Cell Biology and Molecular Medicine, Cardiovascular Research Institute, Rutgers New Jersey Medical School, Newark, NJ, USA.
  79. Sandra and Edward Meyer Cancer Center, New York, NY, USA.
  80. Caryl and Israel Englander Institute for Precision Medicine, New York, NY, USA.
  81. Istituto Veneto di Medicina Molecolare, Padova, Italy.
  82. Department of Biology, University of Padova, Padova, Italy.
  83. Institute of Pharmacology, University of Bern, Bern, Switzerland.
  84. Department of Clinical Immunology and Allergology, Sechenov University, Moscow, Russia.
  85. Laboratory of Molecular Immunology, Institute of Fundamental Medicine and Biology, Kazan Federal University, Kazan, Russia.
  86. The Kennedy Institute of Rheumatology, NDORMS, University of Oxford, Oxford, UK.
  87. Department of Molecular Medicine, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway.
  88. Centre for Cancer Cell Reprogramming, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
  89. Department of Molecular Cell Biology, Institute for Cancer Research, Oslo University Hospital Montebello, Oslo, Norway.
  90. Institute of Molecular Biology and Biotechnology, Foundation for Research and Technology-Hellas, Heraklion, Crete, Greece.
  91. Department of Basic Sciences, School of Medicine, University of Crete, Heraklion, Crete, Greece.
  92. Molecular Cell Biology of Autophagy, The Francis Crick Institute, London, UK.
  93. Department of Genetics, Graduate School of Medicine, Osaka University, Suita, Japan.
  94. Department of Intracellular Membrane Dynamics, Graduate School of Frontier Biosciences, Osaka University, Suita, Japan.
  95. Integrated Frontier Research for Medical Science Division, Institute for Open and Transdisciplinary Research Initiatives (OTRI), Osaka University, Suita, Japan.
  96. Interdisciplinary Research Center on Biology and Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai, China.
  97. Department of Cell Biology, Harvard Medical School, Boston, MA, USA.
  98. Department of Neurology, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  99. Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Department of Pathophysiology, Shanghai Jiao Tong University School of Medicine (SJTU-SM), Shanghai, China.
  100. Department of Dermatology, Yale School of Medicine, New Haven, CT, USA.
  101. Department of Biosciences and Nutrition, Karolinska Institute, Huddinge, Sweden.

PMID: 34459017 PMCID: PMC8488577 DOI: 10.15252/embj.2021108863

Abstract

Autophagy is a core molecular pathway for the preservation of cellular and organismal homeostasis. Pharmacological and genetic interventions impairing autophagy responses promote or aggravate disease in a plethora of experimental models. Consistently, mutations in autophagy-related processes cause severe human pathologies. Here, we review and discuss preclinical data linking autophagy dysfunction to the pathogenesis of major human disorders including cancer as well as cardiovascular, neurodegenerative, metabolic, pulmonary, renal, infectious, musculoskeletal, and ocular disorders.

© 2021 The Authors. Published under the terms of the CC BY 4.0 license.

Keywords: aging; cancer; inflammation; metabolic syndromes; neurodegeneration

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