Modeling Membrane Morphological Change during Autophagosome Formation
Yuji Sakai,
Ikuko Koyama-Honda,
Masashi Tachikawa,
Roland L. Knorr,
Noboru Mizushima
Affiliations
Yuji Sakai
Department of Biochemistry and Molecular Biology, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo 113-0033, Japan; Interdisciplinary Theoretical and Mathematical Sciences (iTHEMS) Program, RIKEN, Wako, Saitama 351-0198, Japan; Corresponding author
Ikuko Koyama-Honda
Department of Biochemistry and Molecular Biology, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo 113-0033, Japan
Masashi Tachikawa
Interdisciplinary Theoretical and Mathematical Sciences (iTHEMS) Program, RIKEN, Wako, Saitama 351-0198, Japan; Institute for Frontier Life and Medical Sciences, Kyoto University, Shogoin Kawahara-cho, Sakyo-ku, Kyoto 606-8507 Japan
Roland L. Knorr
Department of Biochemistry and Molecular Biology, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo 113-0033, Japan; Max Planck Institute of Colloids and Interfaces, Department of Theory & Bio-Systems, 14424 Potsdam, Germany; Max-Planck-Institute of Molecular Plant Physiology, Department of Molecular Physiology, 14424 Potsdam, Germany
Noboru Mizushima
Department of Biochemistry and Molecular Biology, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo 113-0033, Japan; Corresponding author
Summary: 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.
