Interplay of Packing and Flip-flop in Local Bilayer Deformation. How Phosphatidylglycerol Could Rescue Mitochondrial Function in a Cardiolipin-deficient Yeast Mutant
Interplay of Packing and Flip-flop in Local Bilayer Deformation. How Phosphatidylglycerol Could Rescue Mitochondrial Function in a Cardiolipin-deficient Yeast Mutant
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DOI：
10.1016/j.bpj.2014.07.015
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发表时间：
2014-08-19
影响因子：
3.4
通讯作者：
Angelova, Miglena I.
中科院分区：
文献类型：
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作者：
Khalifat, Nada;Rahimi, Mohammad;Angelova, Miglena I.
在之前的工作中，我们已经证明，在含心磷脂的巨大单层囊泡的外部附近，酸微注射产生了空间局部的跨膜pH梯度，导致小管的形成，在梯度消散后收缩。这些小管的形态与线粒体嵴相似。管状效应可归因于外小叶磷脂的直接包装修饰，这是由心磷脂头基的质子化促进的。在这项研究中，我们比较了含有心磷脂的巨型单层囊泡与含有磷脂酰甘油（PG）的巨型单层囊泡的情况。局部酸化也促进后者小管的形成。然而，与含心磷脂的巨型单层囊泡相比，微酸停止注射后，小管更长，珠光明显，寿命更长。我们将这些差异归因于增加单层表面不平衡的额外机制，即局部跨膜pH梯度促进PG向内翻转。采用完全非线性膜模型和几何计算的模拟结果与这一假设一致。有趣的是，在缺乏心磷脂生物合成的酵母突变体中，只有积累磷脂酰甘油的crd1-零突变体显示出显著的线粒体！活动。我们的工作为这种特性提供了一种可能的解释，并进一步强调了特定脂质在线粒体中的突出作用！函数。
In a previous work, we have shown that a spatially localized transmembrane pH gradient, produced by acid micro-injection near the external side of cardiolipin-containing giant unilamellar vesicles, leads to the formation of tubules that retract after the dissipation of this gradient. These tubules have morphologies similar to mitochondrial cristae. The tubulation effect is attributable to direct phospholipid packing modification in the outer leaflet, that is promoted by protonation of cardiolipin head-groups. In this study, we compare the case of cardiolipin-containing giant unilamellar vesicles with that of giant unilamellar vesicles that contain phosphatidylglycerol (PG). Local acidification also promotes formation of tubules in the latter. However, compared with cardiolipin-containing giant unilamellar vesicles the tubules are longer, exhibit a visible pearling, and have a much longer lifetime after acid micro-injection is stopped. We attribute these differences to an additional mechanism that increases monolayer surface imbalance, namely inward PG flip-flop promoted by the local transmembrane pH gradient. Simulations using a fully nonlinear membrane model as well as geometrical calculations are in agreement with this hypothesis. Interestingly, among yeast mutants deficient in cardiolipin biosynthesis, only the crd1-null mutant, which accumulates phosphatidylglycerol, displays significant mitochondria! activity. Our work provides a possible explanation of such a property and further emphasizes the salient role of specific lipids in mitochondria! function.