PUBLICATION
TBK1-Mediated DRP1 Targeting Confers Nucleic Acid Sensing to Reprogram Mitochondrial Dynamics and Physiology
- Authors
- Chen, S., Liu, S., Wang, J., Wu, Q., Wang, A., Guan, H., Zhang, Q., Zhang, D., Wang, X., Song, H., Qin, J., Zou, J., Jiang, Z., Ouyang, S., Feng, X.H., Liang, T., Xu, P.
- ID
- ZDB-PUB-201217-1
- Date
- 2020
- Source
- Molecular Cell 80: 810-827.e7 (Journal)
- Registered Authors
- Keywords
- DRP1, RLR-MAVS, TBK1, antiviral immunity, cell fate determination, innate immunity, mitochondrial dynamics, mitochondrion, nucleic acid sensing, phosphorylation
- MeSH Terms
-
- Adaptor Proteins, Signal Transducing/genetics
- Adaptor Proteins, Signal Transducing/metabolism
- Animals
- DEAD Box Protein 58/genetics
- DEAD Box Protein 58/metabolism
- Dynamins/genetics
- Dynamins/metabolism*
- HCT116 Cells
- HEK293 Cells
- Humans
- Male
- Mice
- Mice, Transgenic
- Mitochondria/physiology*
- Mutation
- Protein Serine-Threonine Kinases/genetics
- Protein Serine-Threonine Kinases/metabolism*
- RNA/genetics
- RNA/metabolism*
- Signal Transduction/genetics
- Zebrafish/genetics
- Zebrafish/metabolism*
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism
- PubMed
- 33171123 Full text @ Mol. Cell
Citation
Chen, S., Liu, S., Wang, J., Wu, Q., Wang, A., Guan, H., Zhang, Q., Zhang, D., Wang, X., Song, H., Qin, J., Zou, J., Jiang, Z., Ouyang, S., Feng, X.H., Liang, T., Xu, P. (2020) TBK1-Mediated DRP1 Targeting Confers Nucleic Acid Sensing to Reprogram Mitochondrial Dynamics and Physiology. Molecular Cell. 80:810-827.e7.
Abstract
Mitochondrial morphology shifts rapidly to manage cellular metabolism, organelle integrity, and cell fate. It remains unknown whether innate nucleic acid sensing, the central and general mechanisms of monitoring both microbial invasion and cellular damage, can reprogram and govern mitochondrial dynamics and function. Here, we unexpectedly observed that upon activation of RIG-I-like receptor (RLR)-MAVS signaling, TBK1 directly phosphorylated DRP1/DNM1L, which disabled DRP1, preventing its high-order oligomerization and mitochondrial fragmentation function. The TBK1-DRP1 axis was essential for assembly of large MAVS aggregates and healthy antiviral immunity and underlay nutrient-triggered mitochondrial dynamics and cell fate determination. Knockin (KI) strategies mimicking TBK1-DRP1 signaling produced dominant-negative phenotypes reminiscent of human DRP1 inborn mutations, while interrupting the TBK1-DRP1 connection compromised antiviral responses. Thus, our findings establish an unrecognized function of innate immunity governing both morphology and physiology of a major organelle, identify a lacking loop during innate RNA sensing, and report an elegant mechanism of shaping mitochondrial dynamics.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping