Nuclear respiratory factor 2 induces SIRT3 expression

F. Kyle Satterstrom, William R. Swindell, Gaëlle Laurent, Sejal Vyas, Martha L. Bulyk, Marcia C. Haigis

Research output: Contribution to journalArticlepeer-review

48 Scopus citations

Abstract

The mitochondrial deacetylase SIRT3 regulates several important metabolic processes. SIRT3 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 SIRT3 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 SIRT3 and genes with closely correlated expression patterns. In vitro, knockdown or overexpression of NRF-2 modulated SIRT3 levels, and the NRF-2α subunit directly bound to the SIRT3 promoter. Our results suggest that NRF-2 is a regulator of SIRT3 expression and may shed light on how SIRT3 is upregulated during nutrient stress.

Original languageEnglish (US)
Pages (from-to)818-825
Number of pages8
JournalAging Cell
Volume14
Issue number5
DOIs
StatePublished - Oct 1 2015
Externally publishedYes

Keywords

  • Calorie restriction
  • Dietary restriction
  • Microarray analysis
  • Nuclear respiratory factor 2
  • SIRT3

ASJC Scopus subject areas

  • Aging
  • Cell Biology

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