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bioRxiv
BIORXIV
bioRxiv
2692-8205
Cold Spring Harbor Laboratory

10.1101/2024.08.19.608723
preprint
1
Article
Dynamins combine mechano-constriction and membrane remodeling to enable two-step mitochondrial fission via a ‘snap-through’ instability
Alimohamadi Haleh http://orcid.org/0000-0001-6576-2426

Luo Elizabeth Wei-Chia
Yang Rena
Gupta Shivam
Nolden Kelsey A
Mandal Taraknath
Hill R. Blake
Wong Gerard C. L.
20 8 2024
2024.08.19.608723https://creativecommons.org/licenses/by-nc-nd/4.0/ This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which allows reusers to copy and distribute the material in any medium or format in unadapted form only, for noncommercial purposes only, and only so long as attribution is given to the creator.
http://biorxiv.org/lookup/doi/10.1101/2024.08.19.608723
nihpp-2024.08.19.608723.pdf
Abstract

Mitochondrial fission is controlled by dynamin proteins, the dysregulation of which is correlated with diverse diseases. Fission dynamins are GTP hydrolysis-driven mechanoenzymes that self-oligomerize into helical structures that constrict membrane to achieve fission, but details are not well understood. However, dynamins can also remodel membranes by inducing negative Gaussian curvature, the type of curvature required for completion of fission. Here, we examine how these drastically different mechanisms synergistically exert their influences on a membrane, via a mechanical model calibrated with small-angle X-ray scattering structural data. We find that free dynamin can trigger a “snap-through instability” that enforces a shape transition from an oligomer-confined cylindrical membrane to a drastically narrower catenoid-shaped neck within the spontaneous hemi-fission regime, in a manner that depends critically on the length of the confined tube. These results indicate how the combination of dynamin assembly, and paradoxically disassembly, can lead to diverse pathways to scission.

Teaser

Dynamin mechano-constriction by assembly and curvature-driven instability by free monomers synergistically drive mitochondrial fission.
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pmc
