Mitochondrial-associated endoplasmic reticulum membranes (MAM) form innate immune synapses and are targeted by

Stacy M Horner1, Helene Minyi Liu, Hae Soo Park

  • 1Department of Immunology, University of Washington School of Medicine, Seattle, WA 98195, USA.

Insights

The mitochondrial-associated membrane (MAM) acts as an immune synapse, coordinating RIG-I and MAVS signaling during viral RNA infection to activate innate immunity.

Area of Science:

  • Immunology
  • Cell Biology
  • Virology

Background:

  • RIG-I is a cytosolic receptor sensing viral RNA to initiate innate immune responses.
  • MAVS, an adaptor protein, localizes to mitochondria and peroxisomes, but its signaling coordination is unclear.

Purpose of the Study:

  • To investigate the role of MAVS localization and signaling coordination in innate immunity.
  • To identify the specific organelle sites involved in MAVS-mediated antiviral signaling.

Main Methods:

  • Utilized cell-based assays to track RIG-I and MAVS localization during RNA virus infection.
  • Investigated the role of the mitochondrial-associated membrane (MAM) in MAVS signaling.
  • Examined the impact of hepatitis C virus NS3/4A protease on MAVS signaling at the MAM.

Main Results:

  • The MAM serves as a critical platform for RIG-I and MAVS interaction during viral infection.
  • MAVS forms a signaling synapse at the MAM, integrating signals from mitochondria and peroxisomes.
  • Hepatitis C virus protease specifically targets MAVS at the MAM to disrupt innate immune signaling.

Conclusions:

  • The MAM functions as an intracellular immune synapse, crucial for orchestrating antiviral innate immunity.
  • Targeting the MAM-mediated immune synapse is a strategy employed by viruses to evade host defenses.

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