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Experimental determination and mathematical modeling of standard shapes of forming autophagosomes

Yuji Sakai (), Satoru Takahashi, Ikuko Koyama-Honda, Chieko Saito and Noboru Mizushima ()
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Yuji Sakai: The University of Tokyo, Bunkyo-ku
Satoru Takahashi: The University of Tokyo, Bunkyo-ku
Ikuko Koyama-Honda: The University of Tokyo, Bunkyo-ku
Chieko Saito: The University of Tokyo, Bunkyo-ku
Noboru Mizushima: The University of Tokyo, Bunkyo-ku

Nature Communications, 2024, vol. 15, issue 1, 1-11

Abstract: Abstract The formation of autophagosomes involves dynamic morphological changes of a phagophore from a flat membrane cisterna into a cup-shaped intermediate and a spherical autophagosome. However, the physical mechanism behind these morphological changes remains elusive. Here, we determine the average shapes of phagophores by statistically investigating three-dimensional electron micrographs of more than 100 phagophores. The results show that the cup-shaped structures adopt a characteristic morphology; they are longitudinally elongated, and the rim is catenoidal with an outwardly recurved shape. To understand these characteristic shapes, we establish a theoretical model of the shape of entire phagophores. The model quantitatively reproduces the average morphology and reveals that the characteristic shape of phagophores is primarily determined by the relative size of the open rim to the total surface area. These results suggest that the seemingly complex morphological changes during autophagosome formation follow a stable path determined by elastic bending energy minimization.

Date: 2024
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DOI: 10.1038/s41467-023-44442-1

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