Agudo-Canalejo Jaime, Knorr Roland L
Rudolf Peierls Centre for Theoretical Physics, University of Oxford, Oxford, UK.
Department of Chemistry, The Pennsylvania State University, University Park, PA, USA.
Methods Mol Biol. 2019;1880:173-188. doi: 10.1007/978-1-4939-8873-0_10.
Autophagy is an intracellular degradation process that employs complex membrane dynamics to isolate and break down cellular components. However, many unanswered questions remain concerning remodeling of autophagic membranes. Here, we focus on the advantages of theoretical modeling to study the formation of autophagosomes and to understand the origin of autophagosomal membranes. Starting from the well-defined geometry of final autophagosomes, we ask the question of how these organelles can be formed by combining various pre-autophagosomal membranes such as vesicles, membrane tubules, or sheets. We analyze the geometric constraints of autophagosome formation by taking the area of the precursor membranes and their internal volume into account. Our results suggest that vesicle fusion contributes little to the formation of autophagosomes. In the second part, we quantify the curvature of the precursors and report that the formation of autophagosomes is associated with a strong relaxation of membrane curvature energy. This effect we find for a wide range of membrane asymmetries. It is especially strong for small distances between both autophagosomal membranes, as observed in vivo. We quantify the membrane bending energies of all precursors by considering membrane asymmetries. We propose that the generation and supply of pre-autophagosomal membranes is one limiting step for autophagosome formation.
自噬是一种细胞内降解过程，它利用复杂的膜动力学来隔离和分解细胞成分。然而，关于自噬膜的重塑仍有许多未解决的问题。在这里，我们关注理论建模在研究自噬体形成以及理解自噬体膜起源方面的优势。从最终自噬体明确的几何形状出发，我们提出一个问题：这些细胞器如何通过结合各种自噬前体膜（如囊泡、膜管或膜片）形成。我们通过考虑前体膜的面积及其内部体积来分析自噬体形成的几何约束。我们的结果表明囊泡融合对自噬体的形成贡献不大。在第二部分，我们对前体的曲率进行了量化，并报告自噬体的形成与膜曲率能的强烈松弛有关。我们在广泛的膜不对称性范围内都发现了这种效应。在体内观察到的情况下，当两个自噬体膜之间的距离较小时，这种效应尤为明显。我们通过考虑膜不对称性来量化所有前体的膜弯曲能。我们提出自噬前体膜的产生和供应是自噬体形成的一个限制步骤。
