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Modulation of Nrf2 and Mitochondrial Function: Pharmacological Implications

Luciano Saso1, Ilker Ates2, Ramazan Tunc3

  • 1Department of Physiology and Pharmacology "Vittorio Erspamer", Sapienza University of Rome, P. le Aldo Moro 5, 00185 Rome, Italy.

Pharmaceuticals (Basel, Switzerland)
|November 27, 2025
PubMed

Insights

The Nuclear factor-2 erythroid-related factor-2 (Nrf2) pathway protects cells from oxidative stress and mitochondrial damage. Activating Nrf2 is a promising strategy to combat diseases linked to mitochondrial dysfunction.

Area of Science:

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Background:

  • Mammals face constant exposure to free radicals, leading to oxidative stress (OS) when ROS overwhelm antioxidant defenses.
  • OS is implicated in severe cell damage and diseases like cancer, Alzheimer's, and heart disease.
  • The Nuclear factor-2 erythroid-related factor-2 (Nrf2) transcription factor regulates cellular antioxidant systems and mitochondrial function.

Purpose of the Study:

  • To review the influence of Nrf2 on oxidative stress.
  • To elucidate how Nrf2 modulates mitochondrial function.
  • To highlight Nrf2's role in cellular systems and its pharmacological implications.

Main Methods:

  • Literature review focusing on Nrf2's role in OS and mitochondrial activity.
  • Analysis of Nrf2's regulatory functions in metabolic pathways.
  • Examination of Nrf2 activator molecules and their effects on mitophagy and mitochondrial permeability.

Main Results:

  • Nrf2 is a critical regulator of cellular metabolism and antioxidant defense.
  • Nrf2 activation protects cells from mitochondrial toxins and OS-related damage.
  • Nrf2 plays a key role in maintaining mitochondrial health and function.

Conclusions:

  • Nrf2 significantly influences oxidative stress and modulates mitochondrial function.
  • Pharmacological activation of Nrf2 is a potential therapeutic strategy for mitochondrial dysfunction.
  • Mitochondrial dysfunction is central to many life-threatening diseases, underscoring Nrf2's importance.
Keywords:
Nrf2ROSantioxidantmitochondrial functionoxidative stress

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