Khalifat Nada, Fournier Jean-Baptiste, Angelova Miglena I, Puff Nicolas
UPMC Univ. Paris 06, Paris, France.
Biochim Biophys Acta. 2011 Nov;1808(11):2724-33. doi: 10.1016/j.bbamem.2011.07.013. Epub 2011 Jul 22.
Cardiolipin is a four-tailed acidic lipid found predominantly within the inner membrane of mitochondria, and is thought to be a key component in determining inner membrane properties and potential. Thus, cardiolipin may be involved in the dynamics of the inner membrane characteristic invaginations (named cristae) that protrude into the matrix space. In previous studies, we showed the possibility to induce, by localized proton flow, a macroscopic cristae-like shape remodeling of an only-lipid model membrane mimicking the inner mitochondrial membrane. In addition, we reported a theoretical model describing the dynamics of a chemically driven membrane shape instability caused by a modification of the plane-shape equilibrium density of the lipids in the membrane. In the present work, we focus on the lipid-packing modifications observed in a model cardiolipin-containing lipid membrane submitted to pH decrease because this is the driving force of the instability. Laurdan fluorescence and ζ-potential measurements show that under pH decrease, membrane surface charge decreases, but that significant modification of the lipid packing is observed only for CL-containing membranes. Our giant unilamellar vesicle experiments also indicate that cristae-like morphologies are only observed for CL-containing lipid membranes. Taken together, these results highlight the fact that only a strong modulation of the lipid packing of the exposed monolayer leads to membrane shape instability and suggest that mitochondrial lipids, in particular the cardiolipin, play a specific role under pH modulation in inner mitochondrial membrane morphology and dynamics.
心磷脂是一种主要存在于线粒体内膜的四尾酸性脂质，被认为是决定内膜性质和电位的关键成分。因此，心磷脂可能参与了内膜特征性内陷（称为嵴）向基质空间突出的动态过程。在之前的研究中，我们表明通过局部质子流有可能诱导模拟线粒体内膜的仅含脂质的模型膜发生宏观的嵴状形状重塑。此外，我们报道了一个理论模型，描述了由膜中脂质平面形状平衡密度改变引起的化学驱动膜形状不稳定性的动态过程。在本工作中，我们关注在pH降低的含心磷脂的脂质模型膜中观察到的脂质堆积修饰，因为这是不稳定性的驱动力。劳丹荧光和ζ电位测量表明，在pH降低时，膜表面电荷减少，但仅在含心磷脂的膜中观察到脂质堆积的显著修饰。我们的巨型单层囊泡实验还表明，仅在含心磷脂的脂质膜中观察到嵴状形态。综上所述，这些结果突出了这样一个事实，即只有对暴露单层的脂质堆积进行强烈调节才会导致膜形状不稳定，并表明线粒体脂质，特别是心磷脂，在pH调节下在线粒体内膜形态和动态中发挥特定作用。
