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Mitochondria mediate septin cage assembly to promote autophagy of Shigella

Sirianni, A; Krokowski, S; Lobato-Márquez, D; Buranyi, S; Pfanzelter, J; Galea, D; Willis, A; ... Mostowy, S; + view all (2016) Mitochondria mediate septin cage assembly to promote autophagy of Shigella. EMBO Reports , 17 (7) pp. 1029-1043. 10.15252/embr.201541832. Green open access

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Abstract

Septins, cytoskeletal proteins with well-characterised roles in cytokinesis, form cage-like structures around cytosolic Shigella flexneri and promote their targeting to autophagosomes. However, the processes underlying septin cage assembly, and whether they influence S. flexneri proliferation, remain to be established. Using single-cell analysis, we show that the septin cages inhibit S. flexneri proliferation. To study mechanisms of septin cage assembly, we used proteomics and found mitochondrial proteins associate with septins in S. flexneri-infected cells. Strikingly, mitochondria associated with S. flexneri promote septin assembly into cages that entrap bacteria for autophagy. We demonstrate that the cytosolic GTPase dynamin-related protein 1 (Drp1) interacts with septins to enhance mitochondrial fission. To avoid autophagy, actin-polymerising Shigella fragment mitochondria to escape from septin caging. Our results demonstrate a role for mitochondria in anti-Shigella autophagy and uncover a fundamental link between septin assembly and mitochondria.

Type: Article
Title: Mitochondria mediate septin cage assembly to promote autophagy of Shigella
Open access status: An open access version is available from UCL Discovery
DOI: 10.15252/embr.201541832
Publisher version: http://dx.doi.org/10.15252/embr.201541832
Language: English
Additional information: Copyright © 2016 The Authors. Published under the terms of the Creative Commons Attribution 4.0 license (CC BY 4.0) (https://creativecommons.org/licenses/by/4.0/), which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Keywords: autophagy; cytoskeleton; mitochondria; septin; Shigella
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Lab for Molecular Cell Bio MRC-UCL
UCL > Provost and Vice Provost Offices > UCL BEAMS
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Maths and Physical Sciences
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Maths and Physical Sciences > Dept of Physics and Astronomy
URI: https://discovery.ucl.ac.uk/id/eprint/1498887
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