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Related Experiment Video

Updated: Oct 29, 2025

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NQO1 Binds and Supports SIRT1 Function.

Peter Tsvetkov1, Julia Adler2, Romano Strobelt2

  • 1Broad Institute of Harvard and MIT, Cambridge, MA, United States.

Frontiers in Pharmacology
|July 8, 2021
PubMed
Summary
This summary is machine-generated.

Silent information regulator 1 (SIRT1) and NAD(P)H dehydrogenase quinone 1 (NQO1) form a regulatory loop. SIRT1 enhances NQO1 levels, and NQO1 mediates SIRT1

Keywords:
NADH/NAD ratioPGC1 alphaSIRT1 activitymitochondria stressquinone oxidoreductase 1

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Area of Science:

  • Cellular Metabolism
  • Molecular Biology
  • Biochemistry

Background:

  • Silent information regulator 2-related enzyme 1 (SIRT1) is an NAD+-dependent deacetylase crucial for metabolic sensing.
  • SIRT1 activity requires NAD+, suggesting a link with NAD+-producing enzymes like NQO1.

Purpose of the Study:

  • To investigate the regulatory relationship between SIRT1 and NQO1.
  • To elucidate the role of NQO1 in SIRT1-mediated cellular responses, particularly during mitochondrial stress.

Main Methods:

  • Assessed the effect of SIRT1 on NQO1 transcription and protein levels.
  • Examined the physical interaction between SIRT1 and NQO1 using a catalytically inactive SIRT1 mutant.
  • Investigated the interaction and cellular localization of NQO1 under mitochondrial inhibition.
  • Evaluated the functional consequences of NQO1 depletion on SIRT1 target gene expression and protective functions.

Main Results:

  • SIRT1 upregulates NQO1 transcription and protein expression.
  • SIRT1 and NQO1 form a physical complex, dependent on SIRT1 enzymatic activity.
  • Mitochondrial inhibition enhances the SIRT1-NQO1 interaction and increases nuclear NQO1.
  • NQO1 depletion impairs SIRT1's transcriptional activity and its protective effects against mitochondrial stress.

Conclusions:

  • SIRT1 and NQO1 form a positive feedback loop, with SIRT1 regulating NQO1 expression.
  • NQO1 binds to SIRT1 and mediates its protective functions during mitochondrial stress.
  • The SIRT1-NQO1 interplay acts as a rheostat for sensing and responding to mitochondrial stress.