阳离子膜活性毒素是蛇和昆虫毒液中最丰富的蛋白质群。眼镜蛇毒素细胞毒素和蜜蜂毒针蜂毒蛋白等阳离子蛋白质以其药理作用而闻名，包括抗癌和抗菌效果，这是由毒素引起的细胞膜和细胞器膜动态和结构的改变所导致的。已经确定这些阳离子毒素会触发人工和天然线粒体膜中非双层脂质相转变的形成。值得注意的是，毒素引起的非双层脂质相形成会在某些条件下增加线粒体ATP合酶活性。这一观察结果为利用阳离子毒素开发治疗因衰老和疾病引起的细胞能量不足的新药提供了一个有趣的途径。这一观察结果还需要对由阳离子蛋白引发的脂质相多态性的分子机制进行彻底研究。本文系统回顾了在人工和生物膜中使用强大的生物物理方法（如共振光谱（31P-、1H-、2H-核磁共振和电子顺磁共振）、发光和差示扫描微量热法）研究阳离子蛋白质引发的非双层脂质相转变的应用。本文讨论了在10-2-10-11秒内由阳离子蛋白质引发的非双层脂质相转变现象，并针对阳离子蛋白质的潜在药理应用进行了探讨。ATP二聚体旁边是由磷脂酰羟胆碱组成的倒转胶束，用于将H+离子从内晶隙输运到基质中。据推测，这种倒转胶束是由高密度的H+离子和丰富赖氨酸残基的阳离子蛋白质触发的，这些阳离子蛋白质与内线粒体膜上保守的赖氨酸残基竞争与磷脂酰羟胆碱结合，扰乱晶节的双层脂质包装。蓝色极性头代表磷脂酰羟胆碱，红色极性头代表晶节膜中的其他磷脂。©2023年。作者（们）独家授权给斯普林格科学+商业传媒有限公司，斯普林格自然出版集团的一部分。

Cationic membrane-active toxins are the most abundant group of proteins in the venom of snakes and insects. Cationic proteins such as cobra venom cytotoxin and bee venom melittin are known for their pharmacological reactions including anticancer and antimicrobial effects which arise from the toxin-induced alteration in the dynamics and structure of plasma membranes and membranes of organelles. It has been established that these cationic toxins trigger the formation of non-bilayer lipid phase transitions in artificial and native mitochondrial membranes. Remarkably, the toxin-induced formation of non-bilayer lipid phase increases at certain conditions mitochondrial ATP synthase activity. This observation opens an intriguing avenue for using cationic toxins in the development of novel drugs for the treatment of cellular energy deficiency caused by aging and diseases. This observation also warrants a thorough investigation of the molecular mechanism(s) of lipid phase polymorphisms triggered by cationic proteins. This article presents a review on the application of powerful biophysical methods such as resonance spectroscopy (31P-, 1H-, 2H-nuclear magnetic resonance, and electron paramagnetic resonance), luminescence, and differential scanning microcalorimetry in studies of non-bilayer lipid phase transitions triggered by cationic proteins in artificial and biological membranes. A phenomenon of the triggered by cationic proteins the non-bilayer lipid phase transitions occurring within 10-2-10-11 s is discussed in the context of potential pharmacological applications of cationic proteins. Next to the ATP dimer is an inverted micelle made of cardiolipin that serves as a vehicle for the transport of H+ ions from the intra-crista space to the matrix. It is proposed that such inverted micelles are triggered by the high density of H+ ions and the cationic proteins rich in lysine residue which compete with the conserved lysine residues of the ATP synthase rotor for binding to cardiolipin in the inner mitochondrial membrane and perturb the bilayer lipid packing of cristae. Phospholipids with a blue polar head represent cardiolipin and those with a red polar head represent other phospholipids found in the crista membrane.© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.