Geometric instability catalyzes mitochondrial fission.
Geometric instability catalyzes mitochondrial fission.
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DOI：
10.1091/mbc.e18-01-0018
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发表时间：
2019-01-01
影响因子：
3.3
通讯作者：
Agrawal A
中科院分区：
文献类型：
--
作者：
Irajizad E;Ramachandran R;Agrawal A
线粒体膜在分裂过程中经历极端的重塑。虽然一些膜挤压蛋白被认为是分裂的关键驱动因素，但越来越多的证据有力地表明，锥形脂在调节线粒体形态和分裂方面发挥着关键作用。然而，蛋白质和脂类协同执行裂变的机制还没有得到定量的研究。在这里，我们对大管状线粒体的挤压进行了计算模拟，并表明蛋白质和圆锥形脂质可以协同作用，触发屈曲不稳定性，实现极端收缩。更值得注意的是，研究表明，锥形脂质可以与不同的裂变蛋白作用，诱导分层不稳定，并产生越来越窄和稳定的收缩。我们认为，这种几何可塑性通过阻止膜在蛋白质聚合和解聚循环中反弹的弹性倾向，为裂变反应赋予了显着的稳健性。我们的体外研究证实了收缩膜小管中的蛋白质-脂质协同作用。总体而言，我们的工作提出了在细胞膜上实现剧烈拓扑重塑的一般机制。
The mitochondrial membrane undergoes extreme remodeling during fission. While a few membrane-squeezing proteins are recognized as the key drivers of fission, there is a growing body of evidence that strongly suggests that conical lipids play a critical role in regulating mitochondrial morphology and fission. However, the mechanisms by which proteins and lipids cooperate to execute fission have not been quantitatively investigated. Here, we computationally model the squeezing of the largely tubular mitochondrion and show that proteins and conical lipids can act synergistically to trigger buckling instability and achieve extreme constriction. More remarkably, the study reveals that the conical lipids can act with different fission proteins to induce hierarchical instabilities and create increasingly narrow and stable constrictions. We reason that this geometric plasticity imparts significant robustness to the fission reaction by arresting the elastic tendency of the membrane to rebound during protein polymerization and depolymerization cycles. Our in vitro study validates protein–lipid cooperativity in constricting membrane tubules. Overall, our work presents a general mechanism for achieving drastic topological remodeling in cellular membranes.