Review

. 2021 Oct 1;40(19):e108863.

doi: 10.15252/embj.2021108863. Epub 2021 Aug 30.

Autophagy in major human diseases

Daniel J Klionsky¹, Giulia Petroni², Ravi K Amaravadi^{3

4}, Eric H Baehrecke⁵, Andrea Ballabio^{6

7

8}, Patricia Boya⁹, José Manuel Bravo-San Pedro^{10

11}, Ken Cadwell^{12

13

14}, Francesco Cecconi^{15

16

17}, Augustine M K Choi^{18

19}, Mary E Choi^{19

20}, Charleen T Chu²¹, Patrice Codogno^{22

23}, Maria Isabel Colombo²⁴, Ana Maria Cuervo^{25

26}, Vojo Deretic^{27

28}, Ivan Dikic^{29

30}, Zvulun Elazar³¹, Eeva-Liisa Eskelinen³², Gian Maria Fimia^{33

34}, David A Gewirtz³⁵, Douglas R Green³⁶, Malene Hansen³⁷, Marja Jäättelä^{38

39}, Terje Johansen⁴⁰, Gábor Juhász^{41

42}, Vassiliki Karantza⁴³, Claudine Kraft^{44

45}, Guido Kroemer^{46

47

48

49

50}, Nicholas T Ktistakis⁵¹, Sharad Kumar^{52

53}, Carlos Lopez-Otin^{54

55}, Kay F Macleod^{56

57}, Frank Madeo^{58

59

60}, Jennifer Martinez⁶¹, Alicia Meléndez^{62

63}, Noboru Mizushima⁶⁴, Christian Münz⁶⁵, Josef M Penninger^{66

67}, Rushika M Perera^{68

69

70}, Mauro Piacentini^{71

72}, Fulvio Reggiori⁷³, David C Rubinsztein^{74

75}, Kevin M Ryan^{76

77}, Junichi Sadoshima⁷⁸, Laura Santambrogio^{2

79

80}, Luca Scorrano^{81

82}, Hans-Uwe Simon^{83

84

85}, Anna Katharina Simon⁸⁶, Anne Simonsen^{87

88

89}, Alexandra Stolz^{29

30}, Nektarios Tavernarakis^{90

91}, Sharon A Tooze⁹², Tamotsu Yoshimori^{93

94

95}, Junying Yuan^{96

97}, Zhenyu Yue⁹⁸, Qing Zhong⁹⁹, Lorenzo Galluzzi^{2

79

80

100

23}, Federico Pietrocola¹⁰¹

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

Review

Autophagy in major human diseases

Daniel J Klionsky et al. EMBO J. 2021.

. 2021 Oct 1;40(19):e108863.

doi: 10.15252/embj.2021108863. Epub 2021 Aug 30.

Authors

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.

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

PubMed Disclaimer

Conflict of interest statement

A.B. is cofounder of CASMA Therapeutics Inc., Advisory Board member of Next Generation Diagnostics and of Avilar Therapeutics. K.C. has received research support from Pfizer, Takeda, Pacific Biosciences, and AbbVie; consulted for or received an honorarium from PureTech Health, Genentech, and AbbVie; and holds U.S. patent 10,722,600 and provisional patents 62/935,035 and 63/157,225. A.M.K.C. is a cofounder, stock holder and serves on the Scientific Advisory Board for Proterris, which develops therapeutic uses for carbon monoxide. A.M.K.C. also has a use patent on CO. G.K is a cofounder and advisor of EverImmune, Samsara Therapeutics, and Therafast Bio as well as advisor for The Longevity Labs (TLL). F.M. is a founder, is advisor, and has equity interests in The Longevity Labs (TLL) and Samara Therapeutics. D.C.R is a consultant for Aladdin Healthcare Technologies SE, Drishti Discoveries, and Nido Biosciences. L.G. has received research funding from Lytix Biopharma and Phosplatin, as well as consulting/advisory honoraria from Boehringer Ingelheim, AstraZeneca, OmniSEQ, Onxeo, The Longevity Labs, Inzen, and the Luke Heller TECPR2 Foundation. RKA is cofounder of Pinpoint Therapeutics and advisor for Deciphera, Sprint Biosciences, Merck, and Immunacell. He gets research funding for clinical trials from Novartis, Bristol Myers Squibb, Pfizer, and Deciphera. J.Y. is a consultant for Denali Therapeutics, Sanofi, and Nido. All other authors have no conflicts of interest to disclose.

Figures

**Figure 1. Common human disorders linked to dysregulated autophagic activity**
Representation of the main organ‐specific (red) and systemic (blue) human illnesses in which autophagy plays a critical role and that are discussed in this review. ALS, amyotrophic lateral sclerosis; COPD, chronic obstructive pulmonary disease; DKD, diabetic kidney disease; NAFLD, non‐alcoholic fatty liver disease; PDB, Paget disease of bone.

**Figure 2. Basic principles of autophagy modulation as a therapeutic strategy for human disease**
In multiple settings including various neurodegenerative conditions, autophagy defects contribute to disease onset and progression, suggesting that autophagy activators may mediate beneficial effects. Conversely, proficient autophagic responses support tumor progression and resistance to therapy, pointing to autophagy inhibition as an appropriate therapeutic approach. In both scenarios, the effect of autophagy modulation on non‐diseased cells must be carefully considered to enable safety and superior therapeutic efficacy.

See this image and copyright information in PMC

References

1. Abdel Fattah E, Bhattacharya A, Herron A, Safdar Z, Eissa NT (2015) Critical role for IL‐18 in spontaneous lung inflammation caused by autophagy deficiency. J Immunol 194: 5407–5416 - PMC - PubMed
1. Abebe T, Mahadevan J, Bogachus L, Hahn S, Black M, Oseid E, Urano F, Cirulli V, Robertson RP (2017) Nrf2/antioxidant pathway mediates beta cell self‐repair after damage by high‐fat diet‐induced oxidative stress. JCI Insight 2: e92854 - PMC - PubMed
1. Aden K, Tran F, Ito GO, Sheibani‐Tezerji R, Lipinski S, Kuiper JW, Tschurtschenthaler M, Saveljeva S, Bhattacharyya J, Häsler Ret al (2018) ATG16L1 orchestrates interleukin‐22 signaling in the intestinal epithelium via cGAS‐STING. J Exp Med 215: 2868–2886 - PMC - PubMed
1. Adolph TE, Tomczak MF, Niederreiter L, Ko H‐J, Böck J, Martinez‐Naves E, Glickman JN, Tschurtschenthaler M, Hartwig J, Hosomi Set al (2013) Paneth cells as a site of origin for intestinal inflammation. Nature 503: 272–276 - PMC - PubMed
1. Aghajan M, Li N, Karin M (2012) Obesity, autophagy and the pathogenesis of liver and pancreatic cancers. J Gastroenterol Hepatol 27(Suppl 2): 10–14 - PMC - PubMed

Publication types

Actions

MeSH terms

Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions

Save citation to file

Email citation

Add to Collections

Add to My Bibliography

Your saved search

Create a file for external citation management software

Your RSS Feed

Autophagy in major human diseases

Affiliations

Autophagy in major human diseases

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

Publication types

MeSH terms

Substances

Grants and funding

LinkOut - more resources

Full Text Sources

Other Literature Sources