Open AccessNuclear respiratory factor 2 induces SIRT 3 expression
Author(s) -
Satterstrom F. Kyle,
Swindell William R.,
Laurent Gaëlle,
Vyas Sejal,
Bulyk Martha L.,
Haigis Marcia C.
Publication year - 2015
Publication title -
aging cell
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.103
H-Index - 140
eISSN - 1474-9726
pISSN - 1474-9718
DOI - 10.1111/acel.12360
Subject(s) - sirt3 , biology , transcription factor , gene knockdown , downregulation and upregulation , microbiology and biotechnology , phenotype , protein subunit , regulator , regulation of gene expression , gene expression , gene , genetics , sirtuin , acetylation
Summary The mitochondrial deacetylase SIRT 3 regulates several important metabolic processes. SIRT 3 is transcriptionally upregulated in multiple tissues during nutrient stresses such as dietary restriction and fasting, but the molecular mechanism of this induction is unclear. We conducted a bioinformatic study to identify transcription factor(s) involved in SIRT 3 induction. Our analysis identified an enrichment of binding sites for nuclear respiratory factor 2 ( NRF ‐2), a transcription factor known to play a role in the expression of mitochondrial genes, in the DNA sequences of SIRT 3 and genes with closely correlated expression patterns. In vitro , knockdown or overexpression of NRF‐2 modulated SIRT 3 levels, and the NRF ‐2α subunit directly bound to the SIRT 3 promoter. Our results suggest that NRF ‐2 is a regulator of SIRT 3 expression and may shed light on how SIRT 3 is upregulated during nutrient stress.