The Role of PARP-1 and PARP-2 Enzymes in Metabolic Regulation and Disease
Open accessAbstract
While originally described as DNA damage repair agents, recent data suggest a role for poly(ADP-ribose) polymerase (PARP) enzymes in metabolic regulation by influencing mitochondrial function and oxidative metabolism. Here we review how PARP activity has a major metabolic impact and the role of PARP-1 and PARP-2 in diverse metabolic complications.
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Among all PARPs, only PARP1, PARP2 and PARP3 localize to the nucleus in response to early DNA damage and have a key role in DNA damage repair.
“Among all the PARPs, only PARP1, PARP2 and PARP3 localize to the nucleus (FIG. 1b) in response to early DNA damage and have a key role in DNA damage repair25–27 (Supplementary Box 2).”
From NAD+ metabolism and its roles in cellular processes during ageing (2021) · cites this paper as [25]
PARP2 activity may influence NAD+ bioavailability.
“PARP2 activity may also influence NAD+ bioavailability25,26.”
From NAD+ metabolism and its roles in cellular processes during ageing (2021) · cites this paper as [25]
PARP1 is the main PARP enzyme in mammalian tissues and consumes NAD+ during catalysis.
“PARP1 is the main PARP enzyme in mammalian tissues and utilize NAD+ during its catalysis”
From A Potent and Specific CD38 Inhibitor Ameliorates Age-Related Metabolic Dysfunction by Reversing Tissue NAD+ Decline (2018) · cites this paper as Bai and Cantó, 2012
Inhibiting PARP1 can raise cellular NAD+ by reducing its degradation.
“several studies have proposed that PARP1 inhibition can be used to promote increases in cellular levels of NAD+ by decreasing its degradation”
From A Potent and Specific CD38 Inhibitor Ameliorates Age-Related Metabolic Dysfunction by Reversing Tissue NAD+ Decline (2018) · cites this paper as Bai and Cantó, 2012
Blocking alternative NAD+ consuming enzymes like PARP-1 is a way to raise NAD+ levels.
“One strategy to increase NAD+ levels consists of the inhibition of alternative NAD+ consuming enzymes, such as poly(ADP-ribose) polymerase-1 (PARP-1) (Bai and Canto, 2012), which is involved in DNA damage detection and repair.”
From Pharmacological Inhibition of poly(ADP-ribose) polymerases improves fitness and mitochondrial function in skeletal muscle (2014) · cites this paper as Bai and Canto, 2012
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- Authors
- Bai, P., & Cantó, C.
- Affiliations
- University of Debrecen (HU)
- Nestlé (Switzerland) (CH)
- Corresponding author
- Bai, Péter
- Cantó, Carles
- Venue
- Cell Metabolism
- Publisher
- Elsevier BV
- Published
- 2012-09
- Volume
- 16
- Issue
- 3
- Pages
- 290-295
- ISSN
- 1550-4131 (ISSN-L)
- OpenAlex
- W2086531857
- Cited by
- 312
- References
- 20
- Citations by year
- 2026: 20 · 2025: 19 · 2024: 27 · 2023: 26 · 2022: 24 · 2021: 26 · 2020: 18 · 2019: 25 · 2018: 20 · 2017: 17 · 2016: 22 · 2015: 21 · 2014: 28 · 2013: 18 · 2012: 1
- FWCI
- 10.75
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell Metabolism (publishedVersion)
- PubMed (publishedVersion)
- University of Debrecen Electronic Archive (University of Debrecen) (submittedVersion)
- Topics
- Health Sciences › Medicine › Oncology › PARP inhibition in cancer therapy
- Health Sciences › Medicine › Geriatrics and Gerontology › Sirtuins and Resveratrol in Medicine
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Keywords
- PARP1, PARP2, poly(ADP-ribose) polymerase, metabolic regulation, mitochondrial function, oxidative metabolism, DNA repair, metabolic disorders
- MeSH terms
- Poly (ADP-Ribose) Polymerase-1, Energy Metabolism, Humans, Metabolic Diseases, Mitochondria, Poly(ADP-ribose) Polymerases, Transcription Factors, Metabolic Networks and Pathways, Sirtuin 1
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