Mitochondria mediate septin cage assembly to promote autophagy of Shigella.
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.
Section of Microbiology, MRC Centre for Molecular Bacteriology and Infection, Imperial College London, London, UK.
Andrea
A
Sirianni
Section of Microbiology, MRC Centre for Molecular Bacteriology and Infection, Imperial College London, London, UK.
Sina
S
Krokowski
Section of Microbiology, MRC Centre for Molecular Bacteriology and Infection, Imperial College London, London, UK.
Damián
D
Lobato-Márquez
Section of Microbiology, MRC Centre for Molecular Bacteriology and Infection, Imperial College London, London, UK.
Stephen
S
Buranyi
Cellular Signalling and Cytoskeletal Function Laboratory, The Francis Crick Institute, Lincoln's Inn Fields Laboratory, London, UK.
Julia
J
Pfanzelter
Section of Microbiology, MRC Centre for Molecular Bacteriology and Infection, Imperial College London, London, UK.
Dieter
D
Galea
Section of Microbiology, MRC Centre for Molecular Bacteriology and Infection, Imperial College London, London, UK.
Alexandra
A
Willis
Quantitative Imaging and NanoBiophysics Group, MRC Laboratory for Molecular Cell Biology, Department of Cell and Developmental Biology, University College London, London, UK.
Siân
S
Culley
Quantitative Imaging and NanoBiophysics Group, MRC Laboratory for Molecular Cell Biology, Department of Cell and Developmental Biology, University College London, London, UK.
Ricardo
R
Henriques
Faculty of Natural Sciences, Department of Life Sciences, MRC Centre for Molecular Bacteriology and Infection, Imperial College London, London, UK.
Gerald
G
Larrouy-Maumus
Department of Pathology, University of Cambridge, Cambridge, UK.
Michael
M
Hollinshead
Section of Virology, St. Mary's Medical School, Imperial College London, London, UK Section of Paediatrics, St. Mary's Medical School, Imperial College London, London, UK.
Vanessa
V
Sancho-Shimizu
Cellular Signalling and Cytoskeletal Function Laboratory, The Francis Crick Institute, Lincoln's Inn Fields Laboratory, London, UK Section of Virology, St. Mary's Medical School, Imperial College London, London, UK.
Michael
M
Way
Section of Microbiology, MRC Centre for Molecular Bacteriology and Infection, Imperial College London, London, UK s.mostowy@imperial.ac.uk.
Serge
0000-0002-7286-6503
S
Mostowy
D001343:Autophagy; D018797:Cell Cycle Proteins / Q000378:metabolism; D002460:Cell Line; D003598:Cytoskeletal Proteins / Q000378:metabolism; D006801:Humans; D008928:Mitochondria / Q000378:metabolism*; D063154:Mitochondrial Dynamics; D024101:Mitochondrial Proteins / Q000378:metabolism; D008954:Models, Biological; D011485:Protein Binding; D058112:Septins / Q000378:metabolism*; D012760:Shigella / Q000502:physiology*
D018797:Cell Cycle Proteins; D003598:Cytoskeletal Proteins; D024101:Mitochondrial Proteins; D058112:Septins
Shigella; autophagy; cytoskeleton; mitochondria; septin