Department of Basic Medical Sciences, Neurosciences and Sense Organs, University of Bari "Aldo Moro", 70124 Bari, Italy.
Department of Clinical and Experimental Medicine, University of Foggia, 71122 Foggia, Italy.
Int J Mol Sci. 2022 Aug 25;23(17):9655. doi: 10.3390/ijms23179655.
The oxidative phosphorylation (OXPHOS) system couples the transfer of electrons to oxygen with pumping of protons across the inner mitochondrial membrane, ensuring the ATP production. Evidence suggests that respiratory chain complexes may also assemble into supramolecular structures, called supercomplexes (SCs). The SCs appear to increase the efficiency/capacity of OXPHOS and reduce the reactive oxygen species (ROS) production, especially that which is produced by complex I. Studies suggest a mutual regulation between complex I and SCs, while SCs organization is important for complex I assembly/stability, complex I is involved in the supercomplex formation. Complex I is a pacemaker of the OXPHOS system, and it has been shown that the PKA-dependent phosphorylation of some of its subunits increases the activity of the complex, reducing the ROS production. In this work, using in ex vivo and in vitro models, we show that the activation of cAMP/PKA cascade resulted in an increase in SCs formation associated with an enhanced capacity of electron flux and ATP production rate. This is also associated with the phosphorylation of the NDUFS4 subunit of complex I. This aspect highlights the key role of complex I in cellular energy production.
氧化磷酸化（OXPHOS）系统将电子传递到氧气与质子跨线粒体内膜泵浦耦联，确保 ATP 的产生。有证据表明，呼吸链复合物也可能组装成超分子结构，称为超级复合物（SCs）。SCs 似乎可以提高 OXPHOS 的效率/能力，并减少活性氧物种（ROS）的产生，特别是由复合物 I 产生的 ROS。研究表明复合物 I 和SCs 之间存在相互调节，而SCs 的组织对于复合物 I 的组装/稳定性很重要，复合物 I 参与了超级复合物的形成。复合物 I 是 OXPHOS 系统的起搏器，已经表明其一些亚基的 PKA 依赖性磷酸化增加了复合物的活性，减少了 ROS 的产生。在这项工作中，我们使用离体和体外模型表明，cAMP/PKA 级联的激活导致与电子通量和 ATP 产生速率增强相关的SCs 形成增加。这也与复合物 I 的 NDUFS4 亚基的磷酸化有关。这一方面强调了复合物 I 在细胞能量产生中的关键作用。
