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Updated: Sep 11, 2025

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ATF4-mediated expression of NOXA is critical for Necroptosis driven by Glucose Deprivation

Sasiprapa Sonkaew1,2, Ruwaida Rajna1, Yeon-Ji Park1

  • 1National Cancer Institute; National Institutes of Health, Laboratory of Immune Cell Biology, Bethesda, MD, USA.

Frontiers in Cell Death
|August 14, 2025
PubMed

Insights

Glucose deprivation induces necroptosis, a cell death pathway. Researchers found the mitochondrial protein Noxa is essential for this process and its expression is regulated by ATF4.

Area of Science:

  • Cellular biology
  • Molecular mechanisms of cell death
  • Metabolic stress responses

Background:

  • Glucose deprivation (GD) is a metabolic stress that triggers necroptosis.
  • Mitochondrial protein Noxa's role in GD-induced necroptosis and mitochondrial DNA release is unclear.
  • Understanding Noxa's function is crucial for targeting necroptosis.

Purpose of the Study:

  • To investigate the role of Noxa in glucose deprivation-induced necroptosis.
  • To elucidate the molecular mechanisms regulating Noxa expression under GD.
  • To explore Noxa as a potential therapeutic target.

Main Methods:

  • Investigated the requirement of Noxa in GD-induced necroptosis.
  • Analyzed the regulation of Noxa expression during GD.
  • Utilized molecular biology techniques to study Noxa and ATF4 interactions.

Main Results:

  • Noxa is essential for the induction of necroptosis under glucose deprivation.
  • Glucose deprivation upregulates Noxa expression.
  • ATF4 is identified as the key transcription factor mediating Noxa upregulation by GD.

Conclusions:

  • Noxa plays a critical role in GD-induced necroptosis.
  • ATF4-mediated upregulation of Noxa is a key regulatory mechanism.
  • Noxa represents a potential therapeutic target for cancer and necroptosis-related diseases.
Keywords:
ATF4Glucose deprivationNecroptosisNoxa

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