Mitochondria mediate septin cage assembly to promote autophagy of Shigella |
| |
| Authors: | Andrea Sirianni Sina Krokowski Damián Lobato‐Márquez Stephen Buranyi Julia Pfanzelter Dieter Galea Alexandra Willis Siân Culley Ricardo Henriques Gerald Larrouy‐Maumus Michael Hollinshead Vanessa Sancho‐Shimizu Michael Way Serge Mostowy |
| |
| Affiliation: | 1. Section of Microbiology, MRC Centre for Molecular Bacteriology and Infection, Imperial College London, London, UK;2. Cellular Signalling and Cytoskeletal Function Laboratory, The Francis Crick Institute, Lincoln's Inn Fields Laboratory, London, UK;3. Quantitative Imaging and NanoBiophysics Group, MRC Laboratory for Molecular Cell Biology, Department of Cell and Developmental Biology, University College London, London, UK;4. Faculty of Natural Sciences, Department of Life Sciences, MRC Centre for Molecular Bacteriology and Infection, Imperial College London, London, UK;5. Department of Pathology, University of Cambridge, Cambridge, UK;6. Section of Virology, St. Mary's Medical School, Imperial College London, London, UK;7. Section of Paediatrics, St. Mary's Medical School, Imperial College London, London, UK |
| |
| 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. |
| |
| Keywords: | autophagy cytoskeleton mitochondria septin
Shigella
|
|
|
