Regulation of Insulin Secretion by SIRT4, a Mitochondrial ADP-ribosyltransferase
Open accessAbstract
Sirtuins are homologues of the yeast transcriptional repressor Sir2p and are conserved from bacteria to humans. We report that human SIRT4 is localized to the mitochondria. SIRT4 is a matrix protein and becomes cleaved at amino acid 28 after import into mitochondria. Mass spectrometry analysis of proteins that coimmunoprecipitate with SIRT4 identified insulindegrading enzyme and the ADP/ATP carrier proteins, ANT2 and ANT3. SIRT4 exhibits no histone deacetylase activity but functions as an efficient ADP-ribosyltransferase on histones and bovine serum albumin. SIRT4 is expressed in islets of Langerhans and colocalizes with insulin-expressing beta cells. Depletion of SIRT4 from insulin-producing INS-1E cells results in increased insulin secretion in response to glucose. These observations define a new role for mitochondrial SIRT4 in the regulation of insulin secretion.
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SIRT4 interacts with adenine nucleotide translocator, possibly regulating the ADP to ATP ratio and mitochondrial physiology.
“SIRT4 interacts with adenine nucleotide translocator, possibly regulating the ADP to ATP ratio and mitochondrial physiology54.”
From Mitochondrial and metabolic dysfunction in ageing and age-related diseases (2022) · cites this paper as [54]
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References 50 · Cited by 422
- Authors
- Ahuja, N., Schwer, B., Carobbio, S., Waltregny, D., North, B. J., Castronovo, V., Maechler, P., & Verdin, E.
- Affiliations
- University of California, San Francisco (US)
- University of Geneva (CH)
- University of Liège (BE)
- Corresponding author
- Verdin, Eric
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2007-11
- Volume
- 282
- Issue
- 46
- Pages
- 33583-33592
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2083434423
- Cited by
- 422
- References
- 50
- Citations by year
- 2026: 3 · 2025: 10 · 2024: 20 · 2023: 24 · 2022: 14 · 2021: 40 · 2020: 22 · 2019: 14 · 2018: 27 · 2017: 12 · 2016: 38 · 2015: 18 · 2014: 27 · 2013: 29 · 2012: 25
- FWCI
- 10.65
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Open Repository and Bibliography (University of Liège) (submittedVersion, other-oa)
- Topics
- Health Sciences › Medicine › Geriatrics and Gerontology › Sirtuins and Resveratrol in Medicine
- Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Keywords
- SIRT4, insulin secretion, ADP-ribosyltransferase, sirtuins, mitochondrial protein localization, insulin-degrading enzyme, adenine nucleotide translocase, ANT2, pancreatic beta cells, pancreatic islets, glucose-stimulated insulin secretion, INS-1E cells, post-translational processing
- MeSH terms
- Insulin Secretion, Cell Line, Glucose, HeLa Cells, Humans, Insulin, Islets of Langerhans, Mitochondria, Plasmids, Mass Spectrometry, Transfection, DNA, Complementary, Microscopy, Confocal, Mitochondrial Proteins, RNA, Small Interfering, ADP Ribose Transferases, Sirtuins, Immunoprecipitation, Insulin-Secreting Cells
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