Mathematical modelling for autophagosome formation

9 Jul 2018, 15:40
New Law School/--107 (University of Sydney)

New Law School/--107

University of Sydney

Oral Presentation Biochemistry and Cell Biology Cellular & tissue processes


Yuji Sakai (The University of Tokyo)


Autophagy is an intracellular degradation process mediated by the autophagosome. The membrane dynamics of autophagosome formation is unique and complicated, which involves development of a small membrane cisterna into a cup-shaped structure and a double membrane spherical structure by closing the edge [1].

In this presentation, we discuss the mechanism of autophagosome formation from a physical point of view. A flat cisterna has a highly-curved rim, which is energetically unstable. As increasing the membrane surface, the rim area also increases. In order to reduce the energy, the cisterna is spontaneously curled by decreasing the rim area. Accordingly, a shape transition occurs suddenly due to the first order transition [2].

However, live-imaging experiments have shown that autophagosome formation takes place gradually and sudden closure of a flat membrane is not observed. We hypothesize the presence of protein(s) that stabilize the highly-curved rim, which enables gradual enclosure. Indeed, several autophagy proteins are present at the rim.

Thus, we consider the effects of the rim-stabilizing proteins on the dynamics of autophagosome formation. We show that the proteins localize at the highly-curved rim and stabilize it. As a result, intermediate cup-shape states appear and the closing dynamics becomes moderate similar to that of autophagosome formation in vivo.

[1] Mizushima 2017, PMID28186333
[2] Knorr et al., 2012, PMID22427874

Primary authors

Yuji Sakai (The University of Tokyo) Dr Ikuko Koyama-Honda (The University of Tokyo) Dr Masashi Tachikawa (RIKEN) Prof. Noboru Mizushima (The University of Tokyo)

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