Mitochondria mediate septin cage assembly to promote autophagy of Shigella
journal contributionposted on 01.10.2020 by 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
Any type of content formally published in an academic journal, usually following a peer-review process.
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.