Abstract
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 insulin-degrading 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 β 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.
Original language | English (US) |
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Pages (from-to) | 33583-33592 |
Number of pages | 10 |
Journal | Journal of Biological Chemistry |
Volume | 282 |
Issue number | 46 |
DOIs | |
State | Published - Nov 16 2007 |
Externally published | Yes |
All Science Journal Classification (ASJC) codes
- Biochemistry
- Molecular Biology
- Cell Biology