论文标题

在自噬体形成过程中建模膜形态变化

Modeling membrane morphological change during autophagosome formation

论文作者

Sakai, Yuji, Koyama-Honda, Ikuko, Tachikawa, Masashi, Knorr, Roland L., Mizushima, Noboru

论文摘要

自噬是一个细胞内降解过程,是由自噬体从头形成介导的。自噬体形成涉及动态形态变化。圆盘形的膜箱长出,弯曲成为杯状结构,最后发展成球形自噬体。我们构建了一个理论模型,该模型整合了推定曲率发生器的膜形态变化和熵分配,我们用来定量研究自噬体形成过程。我们表明,在自噬体形成过程中,膜曲率和曲率发电机的分布稳定了盘和杯形的中间结构,这与体内观察值一致。这些结果表明,具有膜曲率感应特性的各种自噬蛋白通过稳定这些中间结构来控制形态变化。我们的模型提供了一个理解自噬体形成的框架。

Autophagy is an intracellular degradation process that is mediated by de novo formation of autophagosomes. Autophagosome formation involves dynamic morphological changes; a disk-shaped membrane cisterna grows, bends to become a cup-shaped structure, and finally develops into a spherical autophagosome. We have constructed a theoretical model that integrates the membrane morphological change and entropic partitioning of putative curvature generators, which we have used to investigate the autophagosome formation process quantitatively. We show that the membrane curvature and the distribution of the curvature generators stabilize disk- and cup-shaped intermediate structures during autophagosome formation, which is quantitatively consistent with in vivo observations. These results suggest that various autophagy proteins with membrane curvature-sensing properties control morphological change by stabilizing these intermediate structures. Our model provides a framework for understanding autophagosome formation.

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