Modeling membrane morphological change during autophagosome formation

TL;DR

This paper presents a theoretical model that explains how membrane curvature and protein distribution drive the morphological changes during autophagosome formation, aligning with observed cellular structures.

Contribution

The study introduces a quantitative model integrating membrane dynamics and curvature-generating proteins to elucidate autophagosome formation mechanisms.

Findings

Membrane curvature stabilizes intermediate structures.

Protein distribution influences membrane morphology.

Model aligns with in vivo observations.

Abstract

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.