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 Ca2+-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.

中文翻译：

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复合物 IV——线粒体氧化磷酸化的调节中心

ATP 是所有活细胞中的通用能量货币，主要在线粒体中通过氧化磷酸化 (OXPHOS) 合成。呼吸链的最终和限速步骤是细胞色素 c 氧化酶 (COX)，它代表了 OXPHOS 的调节中心。COX 通过各种效应子与其“多余”亚基的结合、可逆磷酸化和亚基异构体的表达来调节。特别令人感兴趣的是 ATP（OXPHOS 的最终产物）对其的反馈抑制。这种“变构 ATP 抑制”磷酸化和二聚体 COX 保持低且健康的线粒体膜电位（松弛状态），并防止已知会导致多种疾病的 ROS（活性氧）的形成。