Dto. Química Física, Universidad Complutense de Madrid, Avenida Complutense s/n, 28040 Madrid, Spain.
Instituto de Investigación Biomédica Hospital Doce de Octubre (imas12), Avenida de Córdoba s/n, 28041 Madrid, Spain.
Biomolecules. 2020 Jul 21;10(7):1085. doi: 10.3390/biom10071085.
Mitochondria are double-membrane organelles that continuously undergo fission and fusion. Outer mitochondrial membrane fusion is mediated by the membrane proteins mitofusin 1 (Mfn1) and mitofusin 2 (Mfn2), carrying a GTP hydrolyzing domain (GTPase) and two coiled-coil repeats. The detailed mechanism on how the GTP hydrolysis allows Mfns to approach adjacent membranes into proximity and promote their fusion is currently under debate. Using model membranes built up as giant unilamellar vesicles (GUVs), we show here that Mfn1 promotes membrane adhesion of apposing lipid vesicles. The adhesion forces were sustained by the GDP-bound state of Mfn1 after GTP hydrolysis. In contrast, the incubation with the GDP:AlF 4 - , which mimics the GTP transition state, did not induce membrane adhesion. Due to the flexible nature of lipid membranes, the adhesion strength depended on the surface concentration of Mfn1 through a cooperative binding mechanism. We discuss a possible scenario for the outer mitochondrial membrane fusion based on the modulated action of Mfn1.
线粒体是双层膜细胞器，不断经历分裂和融合。外膜融合由膜蛋白融合蛋白 1（Mfn1）和融合蛋白 2（Mfn2）介导，它们携带有 GTP 水解结构域（GTPase）和两个卷曲螺旋重复序列。关于 GTP 水解如何使 Mfns 接近相邻膜并促进融合的详细机制目前仍存在争议。使用构建的作为巨大单层囊泡（GUV）的模型膜，我们在这里表明 Mfn1 促进了相邻脂质囊泡的膜粘附。在 GTP 水解后，GDP 结合状态维持了粘附力。相比之下，用 GDP:AlF 4 -孵育，模拟 GTP 过渡态，不会诱导膜粘附。由于脂质膜的柔性性质，粘附强度通过协同结合机制取决于 Mfn1 的表面浓度。我们根据 Mfn1 的调节作用讨论了一种外线粒体膜融合的可能情景。
