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

• Published in: Redox biology Vol. 53; p. 102340
• Main Authors: Xie, Han, Song, Li, Katz, Sagie, Zhu, Jinyu, Liu, Yawen, Tang, Jinping, Cai, Linjun, Hildebrandt, Peter, Han, Xiao Xia
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01-07-2022; Elsevier
• Subjects: Apoptosis; Cytochrome c; Microsomal monooxygenase; Research Paper; Resonance Raman spectroscopy; ROS; Cytochrome c; Microsomal monooxygenase; ROS; Apoptosis; Resonance Raman spectroscopy
• ISSN: 2213-2317; 2213-2317
• DOI: 10.1016/j.redox.2022.102340

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.
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