Bagkos Georgios, Koufopoulos Kostas, Piperi Christina
Department of Biological Chemistry, University of Athens Medical School, Athens, Greece.
Department of Biological Chemistry, University of Athens Medical School, Athens, Greece.
Med Hypotheses. 2014 Aug;83(2):175-81. doi: 10.1016/j.mehy.2014.05.001. Epub 2014 May 17.
Mitochondrial membrane potential (MMP) is the most reliable indicator of mitochondrial function. The MMP value range of -136 to -140mV has been considered optimal for maximum ATP production for all living organisms. Even small changes from the above range result in a large fall in ATP production and a large increase in ROS production. The resulting bioenergetic deregulation is considered as the causative agent for numerous major human diseases. Normalization of MMP value improves mitochondrial function and gives excellent therapeutic results. In order for a systematic effective treatment of these diseases to be developed, a detailed knowledge of the mechanism of MMP production is absolutely necessary. However, despite the long-standing research efforts, a concrete mechanism for MMP production has not been found yet. The present paper proposes a novel mechanism of MMP production based on new considerations underlying the function of the two basic players of MMP production, the electron transport chain (ETC) and the F1F0 ATP synthase. Under normal conditions, MMP is almost exclusively produced by the electron flow through ETC complexes I-IV, creating a direct electric current that stops in subunit II of complex IV and gradually charges MMP. However, upon ETC dysfunction F1F0 ATP synthase reverses its action and starts to hydrolyze ATP. ATP hydrolysis further produces electric energy which is transferred, in the form of a direct electric current, from F1 to F0 where is used to charge MMP. This new model is expected to redirect current experimental research on mitochondrial bioenergetics and indicate new therapeutic schemes for mitochondrial disorders.
线粒体膜电位（MMP）是线粒体功能最可靠的指标。-136至-140mV的MMP值范围被认为是所有生物体产生最大量ATP的最佳范围。即使与上述范围有微小偏差也会导致ATP产量大幅下降和活性氧生成大幅增加。由此产生的生物能量失调被认为是许多主要人类疾病的致病因素。MMP值的正常化可改善线粒体功能并产生优异的治疗效果。为了开发针对这些疾病的系统有效治疗方法，绝对有必要详细了解MMP产生的机制。然而，尽管进行了长期的研究努力，尚未找到MMP产生的具体机制。本文基于对MMP产生的两个基本参与者，即电子传递链（ETC）和F1F0 ATP合酶功能的新思考，提出了一种MMP产生的新机制。在正常情况下，MMP几乎完全由通过ETC复合体I-IV的电子流产生，形成一股直接电流，该电流在复合体IV的亚基II处停止，并逐渐为MMP充电。然而，当ETC功能障碍时，F1F0 ATP合酶会逆转其作用并开始水解ATP。ATP水解进一步产生电能，该电能以直接电流的形式从F1转移到F0，在那里用于为MMP充电。这一新模型有望重新引导当前关于线粒体生物能量学的实验研究，并为线粒体疾病指明新的治疗方案。
