Mitochondria mediate septin cage assembly to promote autophagy of Shigella

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

doi:10.15252/embr.201541832

Mitochondria mediate septin cage assembly to promote autophagy of Shigella

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^*

^*Corresponding author for this work

Randall Centre of Cell & Molecular Biophysics

Research output: Contribution to journal › Article › peer-review

75 Citations (Scopus)

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.

Original language	English
Pages (from-to)	1029-1043
Number of pages	15
Journal	EMBO Reports
Volume	17
Issue number	7
DOIs	https://doi.org/10.15252/embr.201541832
Publication status	Published - 1 Jul 2016

Keywords

autophagy
cytoskeleton
mitochondria
septin
Shigella

Access to Document

10.15252/embr.201541832

Cite this

@article{830f87700f0c492e89879fd6e5211fee,

title = "Mitochondria mediate septin cage assembly to promote autophagy of Shigella",

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.",

keywords = "autophagy, cytoskeleton, mitochondria, septin, Shigella",

author = "Andrea Sirianni and Sina Krokowski and Dami{\'a}n Lobato-M{\'a}rquez and Stephen Buranyi and Julia Pfanzelter and Dieter Galea and Alexandra Willis and Si{\^a}n Culley and Ricardo Henriques and Gerald Larrouy-Maumus and Michael Hollinshead and Vanessa Sancho-Shimizu and Michael Way and Serge Mostowy",

note = "Funding Information: We thank J. Enninga, P. Sansonetti, F.X. Campbell, L. Baxt and I. Rosenshine for Shigella tools. We thank M. Campanella, D. Faccenda and D.W. Hailey for mitochondria tools. We thank D. Judith, S. Tooze and M. Dionne for autophagy tools and discussion. RH and SC work is funded by the Medical Research Council (MR/K015826/1) and Biotechnology and Biological Sciences Research Council (BB/M022374/1). Work in the SM laboratory is supported by a Wellcome Trust Research Career Development Fellowship (WT097411MA) and the Lister Institute of Preventive Medicine. Publisher Copyright: {\textcopyright} 2016 The Authors. Published under the terms of the CC BY 4.0 license",

year = "2016",

month = jul,

day = "1",

doi = "10.15252/embr.201541832",

language = "English",

volume = "17",

pages = "1029--1043",

journal = "EMBO Reports",

issn = "1469-221X",

publisher = "Wiley-Blackwell",

number = "7",

}

TY - JOUR

T1 - Mitochondria mediate septin cage assembly to promote autophagy of Shigella

AU - Sirianni, Andrea

AU - Krokowski, Sina

AU - Lobato-Márquez, Damián

AU - Buranyi, Stephen

AU - Pfanzelter, Julia

AU - Galea, Dieter

AU - Willis, Alexandra

AU - Culley, Siân

AU - Henriques, Ricardo

AU - Larrouy-Maumus, Gerald

AU - Hollinshead, Michael

AU - Sancho-Shimizu, Vanessa

AU - Way, Michael

AU - Mostowy, Serge

N1 - Funding Information: We thank J. Enninga, P. Sansonetti, F.X. Campbell, L. Baxt and I. Rosenshine for Shigella tools. We thank M. Campanella, D. Faccenda and D.W. Hailey for mitochondria tools. We thank D. Judith, S. Tooze and M. Dionne for autophagy tools and discussion. RH and SC work is funded by the Medical Research Council (MR/K015826/1) and Biotechnology and Biological Sciences Research Council (BB/M022374/1). Work in the SM laboratory is supported by a Wellcome Trust Research Career Development Fellowship (WT097411MA) and the Lister Institute of Preventive Medicine. Publisher Copyright: © 2016 The Authors. Published under the terms of the CC BY 4.0 license

PY - 2016/7/1

Y1 - 2016/7/1

N2 - 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.

AB - 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.

KW - autophagy

KW - cytoskeleton

KW - mitochondria

KW - septin

KW - Shigella

UR - http://www.scopus.com/inward/record.url?scp=84977490585&partnerID=8YFLogxK

U2 - 10.15252/embr.201541832

DO - 10.15252/embr.201541832

M3 - Article

C2 - 27259462

AN - SCOPUS:84977490585

SN - 1469-221X

VL - 17

SP - 1029

EP - 1043

JO - EMBO Reports

JF - EMBO Reports

IS - 7

ER -

Mitochondria mediate septin cage assembly to promote autophagy of Shigella

Abstract

Keywords

Access to Document

Other files and links

Fingerprint

Cite this