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Updated: Jun 3, 2026

Deacetylation Assays to Unravel the Interplay between Sirtuins (SIRT2) and Specific Protein-substrates
14:32

Deacetylation Assays to Unravel the Interplay between Sirtuins (SIRT2) and Specific Protein-substrates

Published on: February 27, 2016

SIRT3 opposes reprogramming of cancer cell metabolism through HIF1α destabilization

Lydia W S Finley1, Arkaitz Carracedo, Jaewon Lee

  • 1Department of Pathology, The Paul F. Glenn Labs for the Biological Mechanisms of Aging, Harvard Medical School, Boston, MA 02115, USA.

Cancer Cell
|March 15, 2011
PubMed

Insights

The mitochondrial deacetylase SIRT3 regulates the Warburg effect by destabilizing HIF1α. Loss of SIRT3 promotes cancer cell glycolysis and proliferation, suggesting SIRT3 as a tumor suppressor.

Area of Science:

  • Cancer Biology
  • Cell Metabolism
  • Mitochondrial Function

Background:

  • Tumor cells exhibit the Warburg effect, characterized by high glycolysis even with oxygen, to generate biomass.
  • Metabolic reprogramming is a hallmark of cancer, crucial for tumor growth and survival.

Purpose of the Study:

  • To investigate the role of mitochondrial NAD-dependent deacetylase SIRT3 in regulating the Warburg effect.
  • To elucidate the molecular mechanism by which SIRT3 influences cancer metabolism and proliferation.

Main Methods:

  • Investigated the interaction between SIRT3 and hypoxia-inducible factor-1α (HIF1α).
  • Assessed the impact of SIRT3 expression on reactive oxygen species (ROS) production and HIF1α stability.
  • Analyzed SIRT3 expression in human breast cancer tissues and correlated it with HIF1α target gene expression.
  • Examined the effects of SIRT3 overexpression on glycolysis and proliferation in breast cancer cells.

Main Results:

  • SIRT3 destabilizes HIF1α, a key regulator of glycolytic gene expression.
  • Loss of SIRT3 leads to increased ROS production, promoting HIF1α stabilization.
  • Reduced SIRT3 expression in human breast cancers correlates with elevated HIF1α target gene expression.
  • Overexpression of SIRT3 suppresses glycolysis and proliferation in breast cancer cells.

Conclusions:

  • SIRT3 is a critical regulator of the Warburg effect, acting by destabilizing HIF1α.
  • SIRT3 functions as a metabolic tumor suppressor by repressing glycolysis and cancer cell proliferation.
  • Targeting SIRT3 or its regulatory pathways may offer therapeutic strategies for breast cancer.

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