Regulation of insulin secretion by SIRT4, a mitochondrial ADP-ribosyltransferase.
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.
Mesh Terms:
ADP Ribose Transferases, Cell Line, DNA, Complementary, Glucose, Hela Cells, Humans, Immunoprecipitation, Insulin, Insulin-Secreting Cells, Islets of Langerhans, Mass Spectrometry, Microscopy, Confocal, Mitochondria, Mitochondrial Proteins, Plasmids, RNA, Small Interfering, Sirtuins, Transfection
ADP Ribose Transferases, Cell Line, DNA, Complementary, Glucose, Hela Cells, Humans, Immunoprecipitation, Insulin, Insulin-Secreting Cells, Islets of Langerhans, Mass Spectrometry, Microscopy, Confocal, Mitochondria, Mitochondrial Proteins, Plasmids, RNA, Small Interfering, Sirtuins, Transfection
J. Biol. Chem.
Date: Nov. 16, 2007
PubMed ID: 17715127
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