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
Section of Microbiology, MRC Centre for Molecular Bacteriology and Infection, Imperial College London, London, UK.
Cellular Signalling and Cytoskeletal Function Laboratory, The Francis Crick Institute, Lincoln's Inn Fields Laboratory, London, UK.
EMBO Rep. 2016 Jul;17(7):1029-43. doi: 10.15252/embr.201541832. Epub 2016 Jun 3.
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.
Septin是一种在胞质分裂中具有明确作用的细胞骨架蛋白，它在胞质中的弗氏志贺氏菌周围形成笼状结构，并促进其靶向自噬体。然而，septin笼组装的潜在过程以及它们是否影响弗氏志贺氏菌的增殖，仍有待确定。通过单细胞分析，我们发现septin笼抑制弗氏志贺氏菌的增殖。为了研究septin笼组装的机制，我们使用蛋白质组学方法，发现线粒体蛋白在弗氏志贺氏菌感染的细胞中与septin相关联。令人惊讶的是，与弗氏志贺氏菌相关的线粒体促进septin组装成笼，将细菌包裹起来进行自噬。我们证明，胞质GTP酶动力蛋白相关蛋白1（Drp1）与septin相互作用以增强线粒体分裂。为了避免自噬，聚合肌动蛋白的志贺氏菌会分裂线粒体以逃离septin笼。我们的结果证明了线粒体在抗志贺氏菌自噬中的作用，并揭示了septin组装与线粒体之间的基本联系。
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