In Situ Raman Spectroscopy Reveals Cytochrome c Redox-Controlled Modulation of Mitochondrial Membrane Permeabilization That Triggers Apoptosis

作者：Jinyu Zhu, Jiangnan Zhu, Han Xie, Jinping Tang, Yu Miao, Linjun Cai, Peter Hildebrandt, Xiao Han · 发表于：Nano Letters · 年份：2023 · DOI：10.1021/acs.nanolett.3c04129 · 被引用次数：18 · 研究领域：Mitochondrial Function and Pathology、Spectroscopy Techniques in Biomedical and Chemical Research、Redox biology and oxidative stress

The selective interaction of cytochrome c (Cyt c ) with cardiolipin (CL) is involved in mitochondrial membrane permeabilization, an essential step for the release of apoptosis activators. The structural basis and modulatory mechanism are, however, poorly understood. Here, we report that Cyt c can induce CL peroxidation independent of reactive oxygen species, which is controlled by its redox states. The structural basis of the Cyt c –CL binding was unveiled by comprehensive spectroscopic investigation and mass spectrometry. The Cyt c -induced permeabilization and its effect on membrane collapse, pore formation, and budding are observed by confocal microscopy. Moreover, cytochrome c oxidase dysfunction is found to be associated with the initiation of Cyt c redox-controlled membrane permeabilization. These results verify the significance of a redox-dependent modulation mechanism at the early stage of apoptosis, which can be exploited for the design of cytochrome c oxidase-targeted apoptotic inducers in cancer therapy.