Wayne State University School of Medicine, Detroit, MI, USA.
Adv Exp Med Biol. 2012;748:237-64. doi: 10.1007/978-1-4614-3573-0_10.
The mitochondrial oxidative phosphorylation (OxPhos) system not only generates the vast majority of cellular energy, but is also involved in the generation of reactive oxygen species (ROS), and apoptosis. Cytochrome c (Cytc) and cytochrome c oxidase (COX) represent the terminal step of the electron transport chain (ETC), the proposed rate-limiting reaction in mammals. Cytc and COX show unique regulatory features including allosteric regulation, isoform expression, and regulation through cell signaling pathways. This chapter focuses on the latter and discusses all mapped phosphorylation sites based on the crystal structures of COX and Cytc. Several signaling pathways have been identified that target COX including protein kinase A and C, receptor tyrosine kinase, and inflammatory signaling. In addition, four phosphorylation sites have been mapped on Cytc with potentially large implications due to its multiple functions including apoptosis, a pathway that is overactive in stressed cells but inactive in cancer. The role of COX and Cytc phosphorylation is reviewed in a human disease context, including cancer, inflammation, sepsis, asthma, and ischemia/reperfusion injury as seen in myocardial infarction and ischemic stroke.
线粒体氧化磷酸化 (OxPhos) 系统不仅产生绝大多数细胞能量，还参与活性氧 (ROS) 的产生和细胞凋亡。细胞色素 c (Cytc) 和细胞色素 c 氧化酶 (COX) 代表电子传递链 (ETC) 的末端步骤，是哺乳动物中提出的限速反应。Cytc 和 COX 具有独特的调节特征，包括变构调节、同工型表达和通过细胞信号通路的调节。本章重点介绍后者，并根据 COX 和 Cytc 的晶体结构讨论所有已映射的磷酸化位点。已经确定了几种靶向 COX 的信号通路，包括蛋白激酶 A 和 C、受体酪氨酸激酶和炎症信号通路。此外，已经映射了 Cytc 上的四个磷酸化位点，由于其多种功能，包括细胞凋亡，在应激细胞中过度活跃但在癌症中不活跃，因此具有潜在的重要意义。在人类疾病背景下，包括癌症、炎症、败血症、哮喘和心肌梗死和缺血性中风等缺血/再灌注损伤中，对 COX 和 Cytc 磷酸化的作用进行了综述。
