Related Experiment Video

Updated: Jun 11, 2026

A High Resolution Method to Monitor Phosphorylation-dependent Activation of IRF3
11:44

A High Resolution Method to Monitor Phosphorylation-dependent Activation of IRF3

Published on: January 24, 2016

Tom70 mediates activation of interferon regulatory factor 3 on mitochondria

Xin-Yi Liu1, Bo Wei, He-Xin Shi

  • 1Laboratory of Molecular Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.

Cell Research
|July 15, 2010
PubMed

Insights

Translocases of outer membrane 70 (Tom70) links mitochondrial antiviral signaling (MAVS) to TANK-binding kinase 1 (TBK1) and interferon regulatory factor 3 (IRF3). This interaction is crucial for activating innate immunity against RNA viruses.

Area of Science:

  • Immunology
  • Cell Biology
  • Virology

Background:

  • RNA viruses are detected by RIG-I/MDA5, initiating signaling via MAVS on mitochondria.
  • MAVS activation leads to TBK1/IRF3 activation, crucial for antiviral responses.
  • The precise mechanism of MAVS-mediated TBK1/IRF3 activation remains unclear.

Purpose of the Study:

  • To elucidate the mechanism by which MAVS activates TBK1/IRF3.
  • To identify novel host factors involved in the MAVS signaling pathway.
  • To understand the role of mitochondria in innate antiviral immunity.

Main Methods:

  • Protein-protein interaction studies using co-immunoprecipitation.
  • Gene expression analysis following Tom70 manipulation (ectopic expression/knockdown).
  • Analysis of TBK1 and IRF3 activation and localization.

Main Results:

  • Tom70, a mitochondrial import receptor, interacts with MAVS during RNA virus infection.
  • Tom70 expression levels correlate with IRF3-mediated gene expression.
  • Tom70 bridges Hsp90 (bound to TBK1/IRF3) to MAVS, recruiting TBK1/IRF3 to mitochondria.
  • Disrupting Tom70-Hsp90 interaction impairs TBK1/IRF3 activation and antiviral responses.

Conclusions:

  • Tom70 acts as a key adaptor linking MAVS to the TBK1/IRF3 complex.
  • Mitochondria are integral components of the innate immune system, facilitating antiviral signaling.
  • Tom70 is a critical regulator of host antiviral defense.

More Related Videos

Native Polyacrylamide Gel Electrophoresis Immunoblot Analysis of Endogenous IRF5 Dimerization08:57

Native Polyacrylamide Gel Electrophoresis Immunoblot Analysis of Endogenous IRF5 Dimerization

Published on: October 6, 2019

Measuring Mitochondrial Function of Naïve and Effector CD8 T Cells06:07

Measuring Mitochondrial Function of Naïve and Effector CD8 T Cells

Published on: March 28, 2025

Related Concept Videos

Translocation of Proteins into the Mitochondria01:19

Translocation of Proteins into the Mitochondria

Mitochondrial precursors are translocated to the internal subcompartments via independent mechanisms involving distinct protein machineries called translocases.
Sorting of outer membrane proteins:
Mitochondrial outer membrane proteins are of two types: the transmembrane, beta-barrel porins, and the membrane-anchored, alpha-helical proteins. Beta-barrel porin precursors are translocated by the TOM complex and inserted into the outer mitochondrial membrane by the SAM complex. In contrast,...
MAPK Signaling Cascades01:07

MAPK Signaling Cascades

Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
Energy to Drive Translocation01:37

Energy to Drive Translocation

Mitochondrial protein import is powered by two distinct energy sources: ATP hydrolysis and electrochemical potential across the inner membrane. Newly synthesized precursors are bound by cytosolic chaperones of the Hsp70 family, which guide them to the import receptors on the mitochondrial surface. Utilizing the energy of ATP hydrolysis, Hsp70 chaperones transfer these precursors to the TOM receptors on the mitochondrial outer membrane.
Generally, polypeptides are unfolded by two distinct...
Protein Transport into the Inner Mitochondrial Membrane01:34

Protein Transport into the Inner Mitochondrial Membrane

Nuclear encoded mitochondrial precursors are imported to the inner membrane in a multistep process involving two separate translocons, TIM22 and TIM23. TIM23 is a cation-selective pore that remains closed by the N terminal segment of the protein. Negative charges on the TIM23 act as a receptor for the incoming precursor, pulling the positively charged matrix-targeting sequence for peptide insertion and translocation.
Transport of mitochondrial precursors across the TIM23 channel is driven by...
Mitochondrial Protein Sorting01:39

Mitochondrial Protein Sorting

Mitochondria are double-membrane organelles of the eukaryotes involved in cellular metabolism, signaling, ATP synthesis, and programmed cell death.  Each of these processes requires specific proteins and enzymes that must be correctly sorted to the right mitochondrial subcompartment for the proper functioning of the organelle.
Most of these mitochondrial proteins are encoded by the nucleus and imported to the mitochondria as unfolded or loosely folded precursors. Mitochondrial precursors...
Mitochondrial Precursor Proteins01:39

Mitochondrial Precursor Proteins

Mitochondrial precursors are partially unfolded or loosely folded polypeptide chains. Newly synthesized precursors are inhibited from spontaneously folding into their native conformation by the cytosolic chaperones, heat shock proteins 70 (Hsp70), and mitochondrial import stimulation factors (MSFs). Precursors bound to MSFs are guided to the TOM70-TOM37 receptors, while precursors bound to Hsp70  chaperones are targetted to TOM20-TOM22 receptor complexes.
Most of the mitochondrial precursors...