MAVS polymers smaller than 80 nm induce mitochondrial membrane remodeling and interferon signaling

The FEBS Journal
Ming-Shih HwangYorgo Modis

Abstract

Double-stranded RNA (dsRNA) is a potent proinflammatory signature of viral infection and is sensed primarily by RIG-I-like receptors (RLRs). Oligomerization of RLRs following binding to cytosolic dsRNA activates and nucleates self-assembly of the mitochondrial antiviral-signaling protein (MAVS). In the current signaling model, the caspase recruitment domains of MAVS form helical fibrils that self-propagate like prions to promote signaling complex assembly. However, there is no conclusive evidence that MAVS forms fibrils in cells or with the transmembrane anchor present. We show here with super-resolution light microscopy that MAVS activation by dsRNA induces mitochondrial membrane remodeling. Quantitative image analysis at imaging resolutions as high as 32 nm shows that in the cellular context, MAVS signaling complexes and the fibrils within them are smaller than 80 nm. The transmembrane domain of MAVS is required for its membrane remodeling, interferon signaling, and proapoptotic activities. We conclude that membrane tethering of MAVS restrains its polymerization and contributes to mitochondrial remodeling and apoptosis upon dsRNA sensing.

References

Jan 1, 1987·Ultramicroscopy·M UnserA C Steven
Aug 1, 1982·Journal of Microscopy·W O Saxton, W Baumeister
Mar 21, 1998·Journal of Molecular Biology·L J HarrisA McPherson
Sep 18, 1998·Biochimica Et Biophysica Acta·H Rottenberg, S Wu
Apr 20, 2002·Biophysical Journal·Russell E ThompsonWatt W Webb
Jul 21, 2004·Journal of Computational Chemistry·Eric F PettersenThomas E Ferrin
Aug 30, 2005·Nature Immunology·Taro KawaiShizuo Akira
Sep 13, 2005·Molecular Cell·Liang-Guo XuHong-Bing Shu
Nov 23, 2005·Proceedings of the National Academy of Sciences of the United States of America·Xiao-Dong LiZhijian J Chen
Oct 14, 2006·Science·Andreas PichlmairCaetano Reis e Sousa
Oct 14, 2006·Science·Veit HornungGunther Hartmann
Apr 5, 2007·Nature Protocols·Carlo Riccardi, Ildo Nicoletti
May 1, 2009·PloS One·Yu LeiJenny P-Y Ting
May 26, 2009·Experimental Neurology·Guy PerkinsMark H Ellisman
May 11, 2010·Cell·Evelyn DixitJonathan C Kagan
Aug 17, 2011·Proceedings of the National Academy of Sciences of the United States of America·Stacy M HornerMichael Gale
Sep 20, 2011·Nature Methods·Prabuddha SenguptaJennifer Lippincott-Schwartz
Dec 14, 2011·Proceedings of the National Academy of Sciences of the United States of America·Alys PeisleySun Hur
Jul 31, 2012·Immunity·Mehul S SutharMichael Gale
Apr 30, 2013·Nature Methods·Robert P J NieuwenhuizenBernd Rieger
Jan 17, 2015·Current Opinion in Immunology·Mitsutoshi YoneyamaTakashi Fujita
Jan 23, 2015·Nature Communications·Romain F LaineClemens F Kaminski
May 6, 2015·Current Opinion in Virology·Bin Wu, Sun Hur
Jan 7, 2016·Proceedings of the National Academy of Sciences of the United States of America·Swapnil C DevarkarJoseph Marcotrigiano
Feb 13, 2016·Journal of Cellular and Molecular Medicine·Ana R FerreiraDaniela Ribeiro
Sep 21, 2016·Nature Immunology·Qi ChenZhijian J Chen
Nov 4, 2016·Journal of Virology·M T Sánchez-AparicioA García-Sastre
Apr 16, 2017·The Journal of Biological Chemistry·Charlotte Lässig, Karl-Peter Hopfner
Dec 1, 2017·BMC Bioinformatics·Curtis T RuedenKevin W Eliceiri
Feb 2, 2018·Viruses·Natalia Zamorano CuervoNathalie Grandvaux

Citations

Apr 23, 2020·The Journal of Cell Biology·Jay X Tan, Toren Finkel
Sep 22, 2019·Cells·Dmitry NamgaladzeBernhard Brüne
Mar 20, 2020·Oxidative Medicine and Cellular Longevity·Yarong DuBurong Hu
Dec 10, 2020·Immunity & Ageing : I & a·Alistair V W NunnJimmy D Bell
Apr 28, 2021·The FEBS Journal·Yu-San Huoh, Sun Hur

Methods Mentioned

BETA
light microscopy
fluorescence microscopy
transfections
transfection
nuclear translocation
MDA
Flow cytometry
Assay

Related Concepts

Related Feeds

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis