The first steroidogenic enzyme, cytochrome P450-side-chain-cleavage (SCC), requires electron transport chain (ETC) complexes III and IV to initiate steroid metabolic processes for mammalian survival. ETC complex II, containing succinate dehydrogenase (quinone), acts with the TCA cycle and has no proton pumping capacity. We show that complex II is required for SCC activation through the proton pump, generating an intermediate state for addition of phosphate by succinate. Phosphate anions in the presence of succinate form a stable mitochondrial complex with higher enthalpy (-ΔH) and enhanced activity. Inhibition of succinate action prevents SCC processing at the intermediate state and ablates activity and mitochondrial protein network. This is the first report directly showing that a protein intermediate state is activated by succinate, facilitating the ETC complex II to interact with complexes III and IV for continued mitochondrial metabolic process, suggesting complex II is essential for steroid metabolism regulation.

第一个类固醇生成酶，即细胞色素P450侧链裂解（SCC），需要电子传输链（ETC）复合物III和IV来启动类固醇代谢过程，以实现哺乳动物的生存。包含琥珀酸脱氢酶（醌）的ETC络合物II具有TCA循环功能，并且没有质子泵送能力。我们表明，复杂的II是通过质子泵进行SCC活化所必需的，生成琥珀酸酯添加磷酸盐的中间状态。琥珀酸存在下的磷酸根阴离子形成稳定的线粒体复合物，具有较高的焓（-ΔH）和增强的活性。琥珀酸作用的抑制阻止了SCC在中间状态下进行，并消除了活性和线粒体蛋白网络。这是第一个直接表明琥珀酸激活了蛋白质中间状态的报告，