Electron transfer between cytochrome c and microsomal monooxygenase generates reactive oxygen species that

Han Xie1, Li Song2, Sagie Katz3

  • 1State Key Laboratory of Supramolecular Structure and Materials, College of Chemistry, Jilin University, Changchun, 130012, PR China.

Redox Biology
|May 24, 2022
PubMed

Insights

Reactive oxygen species (ROS) generation is linked to endoplasmic reticulum and mitochondria crosstalk during apoptosis. Oxidized Cytochrome c (Cyt c) binding to microsomal monooxygenase (MMO) accelerates ROS production, driving programmed cell death.

Area of Science:

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Background:

  • Mitochondria and endoplasmic reticulum crosstalk is critical for apoptosis.
  • Reactive oxygen species (ROS) generation is implicated in this process.
  • Cytochrome c (Cyt c) is hypothesized to mediate signaling by interacting with microsomal monooxygenase (MMO).

Purpose of the Study:

  • To investigate the correlation between ROS production and electron transfer between Cyt c and the MMO system.
  • To elucidate the role of Cyt c redox state in ROS generation and apoptosis.
  • To propose a mechanism for Cyt c-mediated apoptosis via the mitochondria-endoplasmic reticulum pathway.

Main Methods:

  • Resonance Raman (RR) spectroscopy was employed to study ROS production.
  • In-situ RR spectroscopy quantified ROS and its interaction with Cyt c.
  • Isolated endoplasmic reticulum and varying Cyt c redox states were utilized.

Main Results:

  • Binding of Cyt c to MMO induces ROS production.
  • RR spectroscopy quantitatively assessed ROS interactions with Cyt c.
  • ROS generation by endoplasmic reticulum is dependent on the redox state of Cyt c, with oxidized Cyt c accelerating apoptosis.

Conclusions:

  • Oxidized Cyt c plays a key role in accelerating apoptosis by inducing ROS production through MMO.
  • Electron transfer from MMO to Cyt c is proposed as a critical step in the apoptotic mitochondria-endoplasmic reticulum pathway.
  • This research provides insights into Cyt c's regulation of apoptotic pathways and potential for antitumor drug development.

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