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

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.

Automated summary

This study investigates the correlation between ROS production and electron transfer between cytochrome c (Cyt c) and the microsomal monooxygenase (MMO) system using resonance Raman spectroscopy. The results reveal that the binding of Cyt c to MMO induces ROS production, which is quantitatively determined by in-situ RR spectroscopy. The research further highlights the important role of oxidized Cyt c in accelerating apoptosis and proposes the involvement of electron transfer in the mitochondria-endoplasmic reticulum pathway. This study provides important insights into the regulation of apoptotic pathways and may have implications in the design of antitumor drugs for cancer therapy.