Autophagy promotes cell and organismal survival by maintaining NAD(H) pools



Sedlackova, Lucia ORCID: 0000-0003-4482-088X, Otten, Elsje ORCID: 0000-0002-8716-3560, Scialo, Filippo, Shapira, David, Kataura, Tetsushi, Carroll, Bernadette, Seranova, Elena, Rabanal-Ruiz, Yoana, Kelly, George, Stefanatos, Rhoda
et al (show 19 more authors) (2020) Autophagy promotes cell and organismal survival by maintaining NAD(H) pools.

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Abstract

Autophagy is an essential catabolic process that promotes clearance of surplus or damaged intracellular components 1 . As a recycling process, autophagy is also important for the maintenance of cellular metabolites during periods of starvation 2 . Loss of autophagy is sufficient to cause cell death in animal models and is likely to contribute to tissue degeneration in a number of human diseases including neurodegenerative and lysosomal storage disorders 3–7 . However, it remains unclear which of the many cellular functions of autophagy primarily underlies its role in cell survival. Here we have identified a critical role of autophagy in the maintenance of nicotinamide adenine dinucleotide (NAD + /NADH) levels. In respiring cells, loss of autophagy caused NAD(H) depletion resulting in mitochondrial membrane depolarisation and cell death. We also found that maintenance of NAD(H) is an evolutionary conserved function of autophagy from yeast to human cells. Importantly, cell death and reduced viability of autophagy-deficient animal models can be partially reversed by supplementation with an NAD(H) precursor. Our study provides a mechanistic link between autophagy and NAD(H) metabolism and suggests that boosting NAD(H) levels may be an effective intervention strategy to prevent cell death and tissue degeneration in human diseases associated with autophagy dysfunction.

Item Type: Article
Divisions: Faculty of Health and Life Sciences
Faculty of Health and Life Sciences > Institute of Systems, Molecular and Integrative Biology
Depositing User: Symplectic Admin
Date Deposited: 04 Oct 2021 10:00
Last Modified: 02 May 2022 18:12
DOI: 10.1101/2020.01.31.928424
Open Access URL: https://www.biorxiv.org/content/10.1101/2020.01.31...
URI: https://livrepository.liverpool.ac.uk/id/eprint/3139242