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Updated: Aug 3, 2026

Simultaneous Measurement of Superoxide/Hydrogen Peroxide and NADH Production by Flavin-containing Mitochondrial Dehydrogenases
08:57

Simultaneous Measurement of Superoxide/Hydrogen Peroxide and NADH Production by Flavin-containing Mitochondrial Dehydrogenases

Published on: February 24, 2018

Mitochondrial function is required for hydrogen peroxide-induced growth factor receptor transactivation and

Kai Chen1, Shane R Thomas, Adam Albano

  • 1Evans Memorial Department of Medicine and Whitaker Cardiovascular Institute, Boston University School of Medicine, Boston, 715 Albany Street, MA 02118, USA.

The Journal of Biological Chemistry
|June 8, 2004
PubMed

Insights

Hydrogen peroxide (H2O2) triggers growth factor receptor signaling via mitochondria. Targeting mitochondria with antioxidants prevents H2O2-induced cell death, revealing mitochondria as key in this specific cellular response.

Area of Science:

  • Cellular signaling
  • Mitochondrial biology
  • Oxidative stress

Background:

  • Growth factor receptor transactivation is an early step in hydrogen peroxide (H2O2)-induced signaling.
  • The precise upstream targets initiating this process remain largely unidentified.

Purpose of the Study:

  • To investigate the role of mitochondria in H2O2-induced growth factor receptor transactivation and downstream signaling.
  • To determine if mitochondrial function is specifically required for H2O2-mediated signaling pathways.

Main Methods:

  • Inhibition of flavin- or heme-containing proteins and mitochondrial inhibitors (rotenone, antimycin A, KCN, CCCP, oligomycin).
  • Generation of mitochondrial DNA-deficient (pseudo-rho(0)) cells.
  • Treatment with mitochondrial-targeted and non-targeted antioxidants.
  • Assessment of epidermal growth factor receptor (EGFR), JNK, Akt, vascular endothelial growth factor receptor-2 (VEGFR-2), and platelet-derived growth factor-beta receptor (PDGFR-beta) activation.
  • Evaluation of H2O2-induced apoptosis and cell death.

Main Results:

  • Inhibition of mitochondrial function or targeting mitochondria with antioxidants abrogated H2O2-induced EGFR transactivation and downstream JNK/Akt signaling.
  • This effect was specific to H2O2, as mitochondrial inhibitors did not affect JNK activation by UV irradiation or tumor necrosis factor-alpha.
  • Mitochondrial involvement was observed for VEGFR-2 and PDGFR-beta transactivation, but not for ligand-induced receptor activation.
  • Mitochondrial-targeted antioxidants protected against H2O2-induced apoptosis and cell death.

Conclusions:

  • Mitochondria act as a proximal target in H2O2-induced signaling pathways.
  • Redox-sensitive mitochondrial events are crucial for H2O2-mediated growth factor receptor transactivation.
  • Mitochondria play a specific, critical role in cellular responses to oxidative stress induced by H2O2.

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