RT Journal Article
SR Electronic
T1 Autophagy promotes cell and organismal survival by maintaining NAD(H) pools
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.01.31.928424
DO 10.1101/2020.01.31.928424
A1 Lucia Sedlackova
A1 Elsje G. Otten
A1 Filippo Scialo
A1 David Shapira
A1 Tetsushi Kataura
A1 Bernadette Carroll
A1 Elena Seranova
A1 Yoana Rabanal-Ruiz
A1 George Kelly
A1 Rhoda Stefanatos
A1 Glyn Nelson
A1 Francesca Urselli
A1 Animesh Acharjee
A1 Niall Kenneth
A1 Sergey Trushin
A1 Tong Zhang
A1 Charles C. Bascom
A1 Ryan Tasseff
A1 Robert J. Isfort
A1 John E. Oblong
A1 Eugenia Trushina
A1 Masaya Imoto
A1 Shinji Saiki
A1 Michael Lazarou
A1 Manolis Papamichos Chronakis
A1 Oliver D.K. Maddocks
A1 Sovan Sarkar
A1 Alberto Sanz
A1 Viktor I. Korolchuk
YR 2020
UL http://biorxiv.org/content/early/2020/02/17/2020.01.31.928424.abstract
AB Autophagy is an essential catabolic process that promotes clearance of surplus or damaged intracellular components1. As a recycling process, autophagy is also important for the maintenance of cellular metabolites during periods of starvation2. 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 disorders3–7. 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.