Electron transfer between cytochrome c and microsomal monooxygenase generates reactive oxygen species that accelerates apoptosis
Han Xie,
Li Song,
Sagie Katz,
Jinyu Zhu,
Yawen Liu,
Jinping Tang,
Linjun Cai,
Peter Hildebrandt,
Xiao Xia Han
Affiliations
Han Xie
State Key Laboratory of Supramolecular Structure and Materials, College of Chemistry, Jilin University, Changchun, 130012, PR China
Li Song
National Engineering Laboratory for AIDS Vaccine, School of Life Science, Jilin University, Changchun, 130012, PR China
Sagie Katz
Department of Chemistry, Technische Universität Berlin, 10623, Berlin, Germany
Jinyu Zhu
State Key Laboratory of Supramolecular Structure and Materials, College of Chemistry, Jilin University, Changchun, 130012, PR China
Yawen Liu
State Key Laboratory of Supramolecular Structure and Materials, College of Chemistry, Jilin University, Changchun, 130012, PR China
Jinping Tang
State Key Laboratory of Supramolecular Structure and Materials, College of Chemistry, Jilin University, Changchun, 130012, PR China
Linjun Cai
National Engineering Laboratory for AIDS Vaccine, School of Life Science, Jilin University, Changchun, 130012, PR China
Peter Hildebrandt
Department of Chemistry, Technische Universität Berlin, 10623, Berlin, Germany; Corresponding author.
Xiao Xia Han
State Key Laboratory of Supramolecular Structure and Materials, College of Chemistry, Jilin University, Changchun, 130012, PR China; Corresponding author.
Generation of reactive oxygen species (ROS) are possibly induced by the crosstalk between mitochondria and endoplasmic reticula, which is physiologically important in apoptosis. Cytochrome c (Cyt c) is believed to play a crucial role in such signaling pathway by interrupting the coupling within microsomal monooxygenase (MMO). In this study, the correlation of ROS production with the electron transfer between Cyt c and the MMO system is investigated by resonance Raman (RR) spectroscopy. Binding of Cyt c to MMO is found to induce the production of ROS, which is quantitatively determined by the in-situ RR spectroscopy reflecting the interactions of Cyt c with generated ROS. The amount of ROS that is produced from isolated endoplasmic reticulum depends on the redox state of the Cyt c, indicating the important role of oxidized Cyt c in accelerating apoptosis. The role of electron transfer from MMO to Cyt c in the apoptotic mitochondria-endoplasmic reticulum pathway is accordingly proposed. This study is of significance for a deeper understanding of how Cyt c regulates apoptotic pathways through the endoplasmic reticulum, and thus may provide a rational basis for the design of antitumor drugs for cancer therapy.
