The multiple functions of cytochromec(cytc) and their regulation in life and death decisions of the mammalian cell go beyond respiration, apoptosis, ROS scavenging, and oxidation of cardiolipine. It has become increasingly evident that cytcis involved in the propagation of mitogenic signals. It has been proposed that the mitogenic signals occur via the PKCδ-retinoic acid signal complex comprising the protein kinase Cδ, the adapter protein Src homologous collagen homolog (p66Shc), and cytc. We showed the importance of retinoic acid in regulating cellular processes monitored by the Raman bands of cytc. To understand the role of retinoids in regulating redox status of cytc, we recorded the Raman spectra and images of cells receiving redox stimuli by retinoic acid at in vitro cell cultures. For these purposes, we incubated bronchial normal epithelial lung (BEpC) and lung cancer cells (A549) with retinoic acid at concentrations of 1, 10, and 50 µM for 24 and 48 h of incubations. The new role of retinoic acid in a change of the redox status of iron ion in the heme group of cytcfrom oxidized Fe3+to reduced Fe2+form may have serious consequences on ATPase effectiveness and aborting the activation of the conventional mitochondrial signaling protein-dependent pathways, lack of triggering programmed cell death through apoptosis, and lack of cytokine induction. To explain the effect of retinoids on the redox status of cytcin the electron transfer chain, we used the quantum chemistry models of retinoid biology. It has been proposed that retinol catalyzes resonance energy transfer (RET) reactions in cytc. The paper suggests that RET is pivotally important for mitochondrial energy homeostasis by controlling oxidative phosphorylation by switching between activation and inactivation of glycolysis and regulation of electron flux in the electron transport chain. The key role in this process is played by protein kinase C δ (PKCδ), which triggers a signal to the pyruvate dehydrogenase complex. The PKCδ-retinoic acid complex reversibly (at normal physiological conditions) or irreversibly (cancer) responds to the redox potential of cytcthat changes with the electron transfer chain flux.
细胞色素c（cytc）在哺乳动物细胞生死抉择中的多重功能及其调控机制，已超越呼吸作用、细胞凋亡、活性氧清除及心磷脂氧化等传统认知。越来越多的证据表明，cytc参与有丝分裂信号的传导。研究提出，有丝分裂信号通过由蛋白激酶Cδ、衔接蛋白Src同源胶原同源物（p66Shc）及cytc构成的PKCδ-视黄酸信号复合体进行传递。我们通过cytc的拉曼谱带监测，揭示了视黄酸在调控细胞过程中的关键作用。为探究类视黄醇对cytc氧化还原状态的调控机制，我们在体外细胞培养体系中记录了经视黄酸氧化还原刺激的细胞拉曼光谱与图像。为此，我们将支气管正常上皮肺细胞（BEpC）与肺癌细胞（A549）分别置于1、10、50 µM浓度的视黄酸中培养24与48小时。研究发现，视黄酸能诱导cytc血红素基团中铁离子氧化还原状态发生从氧化型Fe³⁺到还原型Fe²⁺的转变，这一新功能可能对ATP酶效能产生严重影响，导致经典线粒体信号蛋白依赖通路激活受阻、程序性细胞凋亡无法触发以及细胞因子诱导缺失。为阐释类视黄醇对电子传递链中cytc氧化还原状态的影响，我们采用量子化学模型解析类视黄醇生物学机制。研究提出视黄醇可催化cytc中的共振能量转移反应。本文指出，共振能量转移通过调控糖酵解激活/失活转换及电子传递链电子通量，对线粒体能量稳态具有核心调控作用，其机制涉及控制氧化磷酸化过程。蛋白激酶Cδ在此过程中发挥关键作用，可向丙酮酸脱氢酶复合体传递信号。PKCδ-视黄酸复合体能可逆性（正常生理条件）或不可逆性（癌症状态）响应cytc随电子传递链通量变化的氧化还原电位。
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