Kataura 2022 Dev Cell

Kataura T, Sedlackova L, Otten EG, Kumari R, Shapira D, Scialo F, Stefanatos R, Ishikawa KI, Kelly G, Seranova E, Sun C, Maetzel D, Kenneth N, Trushin S, Zhang T, Trushina E, Bascom CC, Tasseff R, Isfort RJ, Oblong JE, Miwa S, Lazarou M, Jaenisch R, Imoto M, Saiki S, Papamichos-Chronakis M, Manjithaya R, Maddocks ODK, Sanz A, Sarkar S, Korolchuk VI (2022) Autophagy promotes cell survival by maintaining NAD levels. https://doi.org/10.1016/j.devcel.2022.10.008

» Dev Cell 57:2584-98.e11. PMID: 36413951 Open Access

Kataura Tetsushi,  Sedlackova Lucia,  Otten Elsje G,  Kumari Ruchika,  Shapira David,  Scialo Filippo,  Stefanatos Rhoda,  Ishikawa Kei-Ichi,  Kelly George,  Seranova Elena, Sun Congxin,  Maetzel Dorothea,  Kenneth Niall,  Trushin Sergey,  Zhang Tong,  Trushina Eugenia,  Bascom Charles C,  Tasseff Ryan,  Isfort Robert J,  Oblong John E,  Miwa Satomi,  Lazarou Michael,  Jaenisch Rudolf,  Imoto Masaya,  Saiki Shinji,  Papamichos-Chronakis Manolis,  Manjithaya Ravi,  Maddocks Oliver DK,  Sanz Alberto,  Sarkar Sovan,  Korolchuk Viktor I (2022) Dev Cell

Abstract: 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. • Keywords: DNA damage, NAD, PARP, Sirtuins, Ageing, Autophagy, Metabolism, Mitochondria, Mitophagy • Bioblast editor: Plangger M • O2k-Network Lab: UK Newcastle Von Zglinicki T

Labels: MiParea: Respiration, Genetic knockout;overexpression  Pathology: Aging;senescence 

Organism: Mouse  Tissue;cell: Fibroblast  Preparation: Permeabilized cells 

Coupling state: LEAK, OXPHOS  Pathway: N, NS  HRR: Oxygraph-2k 

2022-11