Mitochondria mediate septin cage assembly to promote autophagy of Shigella

作者:Sirianni Andrea; Krokowski Sina; Lobato Marquez Damian; Buranyi Stephen; Pfanzelter Julia; Galea Dieter; Willis Alexandra; Culley Sian; Henriques Ricardo; Larrouy Maumus Gerald; Hollinshead Michael; Sancho Shimizu Vanessa; Way Michael; Mostowy Serge
来源:EMBO Reports, 2016, 17(7): 1029-1043.
DOI:10.15252/embr.201541832

摘要

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 andmitochondria.

  • 出版日期2016-7