STEM Research Center, Chaoyang Kaiwen Academy, Beijing 100018, China.
Belozersky Institute of Physico-Chemical Biology, M.V. Lomonosov Moscow State University, Moscow 119991, Russia.
Toxins (Basel). 2024 Jun 25;16(7):287. doi: 10.3390/toxins16070287.
In this paper, we provide an overview of mitochondrial bioenergetics and specific conditions that lead to the formation of non-bilayer structures in mitochondria. Secondly, we provide a brief overview on the structure/function of cytotoxins and how snake venom cytotoxins have contributed to increasing our understanding of ATP synthesis via oxidative phosphorylation in mitochondria, to reconcile some controversial aspects of the chemiosmotic theory. Specifically, we provide an emphasis on the biochemical contribution of delocalized and localized proton movement, involving direct transport of protons though the F unit of ATP synthase or via the hydrophobic environment at the center of the inner mitochondrial membrane (proton circuit) on oxidative phosphorylation, and how this influences the rate of ATP synthesis. Importantly, we provide new insights on the molecular mechanisms through which cobra venom cytotoxins affect mitochondrial ATP synthesis, mitochondrial structure, and dynamics. Finally, we provide a perspective for the use of cytotoxins as novel pharmacological tools to study membrane bioenergetics and mitochondrial biology, how they can be used in translational research, and their potential therapeutic applications.
在本文中，我们提供了线粒体生物能量学的概述，以及导致线粒体中非双层结构形成的特定条件。其次，我们简要概述了细胞毒素的结构/功能，以及蛇毒细胞毒素如何有助于增进我们对线粒体氧化磷酸化中 ATP 合成的理解，以调和化学渗透理论的一些有争议的方面。具体来说，我们强调了非定域和局域质子运动的生化贡献，包括质子通过 ATP 合酶的 F 单元的直接运输，或通过线粒体内膜中心的疏水环境（质子回路）进行氧化磷酸化，以及这如何影响 ATP 合成的速率。重要的是，我们提供了关于眼镜蛇毒液细胞毒素影响线粒体 ATP 合成、线粒体结构和动力学的分子机制的新见解。最后，我们展望了细胞毒素作为研究膜生物能量学和线粒体生物学的新型药理学工具的用途，以及它们如何在转化研究中得到应用，以及它们的潜在治疗应用。
