Nuclear respiratory factor 2 induces SIRT 3 expression

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.