Mitochondria mediate septin cage assembly to promote autophagy of Shigella. (3rd June 2016)

• Record Type: Journal Article
• Authors: Sirianni, Andrea; Krokowski, Sina; Lobato‐Márquez, Damián; Buranyi, Stephen; Pfanzelter, Julia; Galea, Dieter; Willis, Alexandra; Culley, Siân; Henriques, Ricardo; Larrouy‐Maumus, Gerald; Hollinshead, Michael; Sancho‐Shimizu, Vanessa; Way, Michael; Mostowy, Serge
• Is Part Of: EMBO reports. Volume 17:Number 7(2016:Jul.)
• Page Start: 1029
• Page End: 1043
• Publication Date: 2016-06-03
• Subjects: autophagy -- cytoskeleton -- mitochondria -- septin -- Shigella; Molecular biology -- Periodicals; Molecular Biology -- Periodicals; Molecular biology; Periodicals; 572.8
• DOI: 10.15252/embr.201541832
• Languages: English
• ISSNs: 1469-221X

Abstract

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. Synopsis: This study shows a close relationship between mitochondria and the assembly of septin cages around Shigella flexneri in infected mammalian cells, uncovering an unexpected role for mitochondria in antibacterial autophagy and host defence. Septin cages restrict the proliferation of cytosolic Shigella flexneri in mammalian cells. Mitochondria promote septin cage assembly and Shigella entrapment for autophagy. Dynamin‐related protein 1 (Drp1) interacts with septins to enhance mitochondrial fission. In order to avoid autophagy, Shigella fragment mitochondria to escape from septin cage entrapment. Abstract : This study shows a close relationship between mitochondria and the assembly of septin cages around Shigella flexneri in infected mammalian cells, uncovering an unexpected role for mitochondria in antibacterial autophagy and host defence.