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MAVS polymers smaller than 80 nm induce mitochondrial membrane remodeling and interferon signaling
Author(s) -
Hwang MingShih,
Boulanger Jérôme,
Howe Jonathan D.,
Albecka Anna,
Pasche Mathias,
Mureşan Leila,
Modis Yorgo
Publication year - 2019
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/febs.14772
Subject(s) - microbiology and biotechnology , interferon , transmembrane protein , biology , signal transduction , cytosol , rna silencing , mitochondrion , chemistry , rna , receptor , rna interference , biochemistry , virology , gene , enzyme
Double‐stranded RNA (ds RNA ) is a potent proinflammatory signature of viral infection and is sensed primarily by RIG ‐I‐like receptors ( RLR s). Oligomerization of RLR s following binding to cytosolic ds RNA 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 ds RNA 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 ds RNA sensing.