Sirtuin activation as a therapeutic approach against inborn errors of metabolism
Open accessAbstract
Protein acylation has emerged as a large family of post translational modifications in which an acyl group can alter the function of a wide variety of proteins, especially in response to metabolic stress. The acylation state is regulated through reversible acylation/deacylation. Acylation occurs enzymatically or non-enzymatically, and responds to acyl-CoA levels. Deacylation on the other hand is controlled through the NAD(+)-dependent sirtuin proteins. In several inborn errors of metabolism (IEMs), accumulation of acyl-CoAs, due to defects in amino acid and fatty acid metabolic pathways, can lead to hyperacylation of proteins. This can have a direct effect on protein function and might play a role in pathophysiology. In this review we describe several mouse and cell models for IEM that display high levels of lysine acylation. Furthermore, we discuss how sirtuins serve as a promising therapeutic target to restore acylation state and could treat IEMs. In this context we examine several pharmacological sirtuin activators, such as resveratrol, NAD(+) precursors and PARP and CD38 inhibitors.
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Acetylation of mitochondrial proteins propagates metabolic inflexibility and deacetylation promotes metabolic flexibility.
“Acetylation of mitochondrial proteins propagates metabolic inflexibility and deacetylation promotes metabolic flexibility (178, 259).”
From Metabolic Flexibility as an Adaptation to Energy Resources and Requirements in Health and Disease (2018) · cites this paper as [259]
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References 110 · Cited by 11
- Authors
- Bleeker, J. C., & Houtkooper, R. H.
- Affiliations
- Amsterdam UMC Location University of Amsterdam (NL)
- Corresponding author
- Houtkooper, Riekelt H.
- Venue
- Journal of Inherited Metabolic Disease
- Publisher
- Wiley
- Published
- 2016-05-04
- Volume
- 39
- Issue
- 4
- Pages
- 565-572
- ISSN
- 0141-8955 (ISSN-L)
- 1573-2665
- PMC
- PMC4920849
- OpenAlex
- W2346524469
- Cited by
- 11
- References
- 110
- Citations by year
- 2023: 1 · 2022: 1 · 2021: 2 · 2019: 1 · 2018: 2 · 2017: 3 · 2016: 1
- FWCI
- 0.24
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Inherited Metabolic Disease (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Pure Amsterdam UMC (publishedVersion, cc-by)
- Data Archiving and Networked Services (DANS) (submittedVersion, other-oa)
- Utrecht University Repository (Utrecht University) (submittedVersion, other-oa)
- Funders
- H2020 European Research Council (638290)
- Topics
- Health Sciences › Medicine › Geriatrics and Gerontology › Sirtuins and Resveratrol in Medicine
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Metabolism and Genetic Disorders
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Genetic Neurodegenerative Diseases
- Keywords
- sirtuins, inborn errors of metabolism, protein acylation, lysine acylation, sirtuin activators, resveratrol, NAD+ precursors, PARP inhibitors, CD38 inhibitors, metabolic stress, therapeutic target
- MeSH terms
- Acyl Coenzyme A, Acylation, Animals, Humans, Metabolism, Inborn Errors, Protein Processing, Post-Translational, Sirtuins, Mice, Molecular Targeted Therapy
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