Fachbereich Chemie/Biochemie, Philipps-University Marburg, Germany.
Mitochondrion. 2021 May;58:296-302. doi: 10.1016/j.mito.2020.10.004. Epub 2020 Oct 15.
ATP, the universal energy currency in all living cells, is mainly synthesized in mitochondria by oxidative phosphorylation (OXPHOS). The final and rate limiting step of the respiratory chain is cytochrome c oxidase (COX) which represents the regulatory center of OXPHOS. COX is regulated through binding of various effectors to its "supernumerary" subunits, by reversible phosphorylation, and by expression of subunit isoforms. Of particular interest is its feedback inhibition by ATP, the final product of OXPHOS. This "allosteric ATP-inhibition" of phosphorylated and dimeric COX maintains a low and healthy mitochondrial membrane potential (relaxed state), and prevents the formation of ROS (reactive oxygen species) which are known to cause numerous diseases. Excessive work and stress abolish this feedback inhibition of COX by Ca-activated dephosphorylation which leads to monomerization and movement of NDUFA4 from complex I to COX with higher rates of COX activity and ATP synthesis (active state) but increased ROS formation and decreased efficiency.
在所有活细胞中，三磷酸腺苷（ATP）是通用的能量货币，主要通过氧化磷酸化（OXPHOS）在线粒体中合成。呼吸链的最后和限速步骤是细胞色素 c 氧化酶（COX），它代表 OXPHOS 的调节中心。COX 通过与“多余”亚基结合各种效应物、可逆磷酸化和同工型亚基的表达来调节。特别值得关注的是它对 OXPHOS 的最终产物 ATP 的反馈抑制。磷酸化和二聚 COX 的这种“变构 ATP 抑制”可保持低而健康的线粒体膜电位（松弛状态），并防止众所周知会导致许多疾病的活性氧（ROS）的形成。过度的工作和压力会通过 Ca 激活的去磷酸化来消除 COX 的这种反馈抑制，导致 NDUFA4 从复合物 I 向 COX 的单体化和运动，从而增加 COX 活性和 ATP 合成的速率（活跃状态），但增加 ROS 的形成和降低效率。
