Autophagy promotes cell survival by maintaining NAD levels.

Animals Mice Humans Cell Survival NAD Saccharomyces cerevisiae Autophagy Cell Death
DNA damage NAD PARP Sirtuins ageing autophagy metabolism mitochondria mitophagy

Journal

Developmental cell
ISSN: 1878-1551
Titre abrégé: Dev Cell
Pays: United States
ID NLM: 101120028

Informations de publication

Date de publication:
21 11 2022
Historique:
received: 08 02 2022
revised: 20 09 2022
accepted: 24 10 2022
entrez: 22 11 2022
pubmed: 23 11 2022
medline: 25 11 2022
Statut: ppublish

Résumé

Autophagy is an essential catabolic process that promotes the clearance of surplus or damaged intracellular components. Loss of autophagy in age-related human pathologies contributes to tissue degeneration through a poorly understood mechanism. Here, we identify an evolutionarily conserved role of autophagy from yeast to humans in the preservation of nicotinamide adenine dinucleotide (NAD) levels, which are critical for cell survival. In respiring mouse fibroblasts with autophagy deficiency, loss of mitochondrial quality control was found to trigger hyperactivation of stress responses mediated by NADases of PARP and Sirtuin families. Uncontrolled depletion of the NAD(H) pool by these enzymes ultimately contributed to mitochondrial membrane depolarization and cell death. Pharmacological and genetic interventions targeting several key elements of this cascade improved the survival of autophagy-deficient yeast, mouse fibroblasts, and human neurons. Our study provides a mechanistic link between autophagy and NAD metabolism and identifies targets for interventions in human diseases associated with autophagic, lysosomal, and mitochondrial dysfunction.

Identifiants

DOI: 10.1016/j.devcel.2022.10.008 PMID: 36413951
pubmed: 36413951
pii: S1534-5807(22)00760-2
doi: 10.1016/j.devcel.2022.10.008
pii:
doi:

Substances chimiques

NAD 0U46U6E8UK

Types de publication

Journal Article Research Support, U.S. Gov't, Non-P.H.S. Research Support, N.I.H., Extramural

Langues

eng

Sous-ensembles de citation

IM

Pagination

2584-2598.e11

Subventions

Organisme : Medical Research Council
ID : MR/P020941/1
Pays : United Kingdom
Organisme : NIA NIH HHS
ID : RF1 AG055549
Pays : United States
Organisme : NINDS NIH HHS
ID : UG3 NS113776
Pays : United States

Commentaires et corrections

Type : CommentIn

Informations de copyright

Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of interests C.C.B., R.T., R.J.I., and J.E.O. are employees of The Procter & Gamble Company, USA. R.J. is the cofounder of Fate Therapeutics, Fulcrum Therapeutics, and Omega Therapeutics and adviser to Dewpoint Therapeutics. E.S. is founder of NMN Bio. V.I.K. is a Scientific Advisor for Longaevus Technologies.

Auteurs

Tetsushi Kataura (T)

Biosciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne NE4 5PL, UK; Department of Biosciences and Informatics, Keio University, Yokohama, Kanagawa 223-8522, Japan; Department of Neurology, Juntendo University School of Medicine, Bunkyo, Tokyo 113-8421, Japan.

Lucia Sedlackova (L)

Biosciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne NE4 5PL, UK.

Elsje G Otten (EG)

Biosciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne NE4 5PL, UK.

Ruchika Kumari (R)

Autophagy lab, Molecular Biology and Genetics Unit, Jawaharlal Nehru Centre for Advanced Scientific Research (JNCASR), Jakkur, Bangalore 560064, India.

David Shapira (D)

Biosciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne NE4 5PL, UK.

Filippo Scialo (F)

Biosciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne NE4 5PL, UK.

Rhoda Stefanatos (R)

Biosciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne NE4 5PL, UK; Wellcome Centre for Mitochondrial Research, Newcastle University, Newcastle upon Tyne, UK; School of Molecular Biosciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow G12 8QQ, UK.

Kei-Ichi Ishikawa (KI)

Department of Neurology, Juntendo University School of Medicine, Bunkyo, Tokyo 113-8421, Japan; Center for Genomic and Regenerative Medicine, Juntendo University Graduate School of Medicine, Bunkyo, Tokyo 113-8421, Japan.

George Kelly (G)

Biosciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne NE4 5PL, UK.

Elena Seranova (E)

Institute of Cancer and Genomic Sciences, Institute of Biomedical Research, College of Medical and Dental Sciences, University of Birmingham, Birmingham B15 2TT, UK.

Congxin Sun (C)

Institute of Cancer and Genomic Sciences, Institute of Biomedical Research, College of Medical and Dental Sciences, University of Birmingham, Birmingham B15 2TT, UK.

Dorothea Maetzel (D)

Whitehead Institute for Biomedical Research, Massachusetts Institute of Technology, Cambridge, MA 02142, USA.

Niall Kenneth (N)

Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool L69 7BE, UK.

Sergey Trushin (S)

Department of Neurology, Mayo Clinic, 200 First St. SW, Rochester, MN 55905, USA.

Tong Zhang (T)

Institute of Cancer Sciences, University of Glasgow, Glasgow G61 1QH, UK; Novartis Institutes for Biomedical Research, Shanghai, China.

Eugenia Trushina (E)

Department of Neurology, Mayo Clinic, 200 First St. SW, Rochester, MN 55905, USA; Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, 200 First St. SW, Rochester, MN 55905, USA.

Charles C Bascom (CC)

The Procter & Gamble Company, Cincinnati, OH 45040, USA.

Ryan Tasseff (R)

The Procter & Gamble Company, Cincinnati, OH 45040, USA.

Robert J Isfort (RJ)

The Procter & Gamble Company, Cincinnati, OH 45040, USA.

John E Oblong (JE)

The Procter & Gamble Company, Cincinnati, OH 45040, USA.

Satomi Miwa (S)

Biosciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne NE4 5PL, UK.

Michael Lazarou (M)

Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Melbourne, VIC 3800, Australia; Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia.

Rudolf Jaenisch (R)

Whitehead Institute for Biomedical Research, Massachusetts Institute of Technology, Cambridge, MA 02142, USA; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02142, USA.

Masaya Imoto (M)

Department of Biosciences and Informatics, Keio University, Yokohama, Kanagawa 223-8522, Japan; Division for Development of Autophagy Modulating Drugs, Juntendo University Graduate School of Medicine, Bunkyo, Tokyo 113-8421, Japan.

Shinji Saiki (S)

Department of Neurology, Juntendo University School of Medicine, Bunkyo, Tokyo 113-8421, Japan; Division for Development of Autophagy Modulating Drugs, Juntendo University Graduate School of Medicine, Bunkyo, Tokyo 113-8421, Japan.

Manolis Papamichos-Chronakis (M)

Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool L69 7BE, UK.

Ravi Manjithaya (R)

Autophagy lab, Molecular Biology and Genetics Unit, Jawaharlal Nehru Centre for Advanced Scientific Research (JNCASR), Jakkur, Bangalore 560064, India.

Oliver D K Maddocks (ODK)

Institute of Cancer Sciences, University of Glasgow, Glasgow G61 1QH, UK.

Alberto Sanz (A)

School of Molecular Biosciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow G12 8QQ, UK.

Sovan Sarkar (S)

Institute of Cancer and Genomic Sciences, Institute of Biomedical Research, College of Medical and Dental Sciences, University of Birmingham, Birmingham B15 2TT, UK. Electronic address: s.sarkar@bham.ac.uk.

Viktor I Korolchuk (VI)

Biosciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne NE4 5PL, UK. Electronic address: viktor.korolchuk@newcastle.ac.uk.

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › Autophagy promotes cell survival by...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Autophagy promotes cell survival by...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Autophagy promotes cell survival by...
questionsmedicales.fr › Phénomènes physiologiques cellulaires › Survie cellulaire › Autophagy promotes cell survival by...
questionsmedicales.fr › Acides nucléiques, nucléotides et nucléosides › Nucléotides › Ribonucléotides › Nucléotides adényliques › NAD › Autophagy promotes cell survival by...
questionsmedicales.fr › Eucaryotes › Champignons › Levures › Saccharomyces › Saccharomyces cerevisiae › Autophagy promotes cell survival by...
questionsmedicales.fr › Phénomènes physiologiques cellulaires › Autophagie › Autophagy promotes cell survival by...
questionsmedicales.fr › Phénomènes physiologiques cellulaires › Mort cellulaire › Autophagy promotes cell survival by...