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Lookup NU author(s): Lucy Sedlackova,
Dr Tetsushi Kataura,
Dr Viktor Korolchuk
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© 2023 Informa UK Limited, trading as Taylor & Francis Group.Age-related human pathologies present with a multitude of molecular and metabolic phenotypes, which individually or synergistically contribute to tissue degeneration. However, current lack of understanding of the interdependence of these molecular pathologies limits the potential range of existing therapeutic intervention strategies. In our study, we set out to understand the chain of molecular events, which underlie the loss of cellular viability in macroautophagy/autophagy deficiency associated with aging and age-related disease. We discover a novel axis linking autophagy, a cellular waste disposal pathway, and a metabolite, nicotinamide adenine dinucleotide (NAD). The axis connects multiple organelles, molecules and stress response pathways mediating cellular demise when autophagy becomes dysfunctional. By elucidating the steps on the path from efficient mitochondrial recycling to NAD maintenance and ultimately cell viability, we highlight targets potentially receptive to therapeutic interventions in a range of genetic and age-related diseases associated with autophagy dysfunction. Abbreviations: IMM: inner mitochondrial membrane; NAD: nicotinamide dinucleotide; OXPHOS: oxidative phosphorylation; PARP: poly(ADP-ribose) polymerase; ROS: reactive oxygen species.
Author(s): Sedlackova L, Kataura T, Sarkar S, Korolchuk VI
Publication type: Article
Publication status: Published
Pages: epub ahead of print
Online publication date: 01/02/2023
Acceptance date: 03/01/2023
ISSN (print): 1554-8627
ISSN (electronic): 1554-8635
Publisher: Taylor and Francis Ltd.
PubMed id: 36727253
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