NAD + : The convergence of DNA repair and mitophagy
Open accessAbstract
ATM is a 350 kDa serine/threonine kinase best known for its role in DNA repair and multiple cellular homeostasis pathways. Mutation in ATM causes the disease ataxia telangiectasia (A-T) with clinical features including ataxia, severe cerebellar atrophy and Purkinje cell loss. In a cross-species study, using primary rat neurons, the roundworm C. elegans, and a mouse model of A-T, we showed that loss of ATM induces mitochondrial dysfunction and compromised mitophagy due to NAD+ insufficiency. Remarkably, NAD+ repletion mitigates both the DNA repair defect and mitochondrial dysfunction in ATM-deficient neurons. In C. elegans, NAD+ repletion can clear accumulated dysfunctional mitochondria through restoration of compromised mitophagy via upregulation of DCT-1. Thus, NAD+ ties together DNA repair and mitophagy in neuroprotection and intimates immediate translational applications for A-T and related neurodegenerative DNA repair-deficient diseases.
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Depletion of NAD+ in aging cells is one of the major causes of aging and degenerative disease.
“It is now recognized that one of the major causes of aging and degenerative disease is the depletion of NAD+ in aging cells [87,88,89,90,91,92].”
From The mitochondrial permeability transition: Nexus of aging, disease and longevity (2021) · cites this paper as [89]
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- Authors
- Fang, E. F., & Bohr, V. A.
- Affiliations
- National Institute on Aging (US)
- Corresponding author
- Fang, Evandro F.
- Bohr, Vilhelm A.
- Venue
- Autophagy
- Publisher
- Informa UK Limited
- Published
- 2016-12-27
- Volume
- 13
- Issue
- 2
- Pages
- 442-443
- ISSN
- 1554-8627 (ISSN-L)
- 1554-8635
- PMC
- PMC5324847
- OpenAlex
- W2559920378
- Cited by
- 45
- References
- 0
- Citations by year
- 2026: 1 · 2025: 7 · 2023: 2 · 2022: 7 · 2021: 7 · 2020: 9 · 2019: 3 · 2018: 6 · 2017: 3
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Autophagy (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Institute on Aging
- Topics
- Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
- Health Sciences › Medicine › Geriatrics and Gerontology › Sirtuins and Resveratrol in Medicine
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Keywords
- NAD+, ATM kinase, ataxia telangiectasia, DNA repair, mitophagy, mitochondrial dysfunction, neuroprotection, neurodegenerative diseases, Purkinje cells, Caenorhabditis elegans, rat neurons
- MeSH terms
- Animals, Ataxia Telangiectasia, Autophagy, DNA Repair, Models, Biological, NAD, Signal Transduction, Caenorhabditis elegans, Mice, Mitophagy, Ataxia Telangiectasia Mutated Proteins
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