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

Publication ,  Journal Article
Horner, SM; Liu, HM; Park, HS; Briley, J; Gale, M
Published in: Proc Natl Acad Sci U S A
August 30, 2011

RIG-I is a cytosolic pathogen recognition receptor that engages viral RNA in infected cells to trigger innate immune defenses through its adaptor protein MAVS. MAVS resides on mitochondria and peroxisomes, but how its signaling is coordinated among these organelles has not been defined. Here we show that a major site of MAVS signaling is the mitochondrial-associated membrane (MAM), a distinct membrane compartment that links the endoplasmic reticulum to mitochondria. During RNA virus infection, RIG-I is recruited to the MAM to bind MAVS. Dynamic MAM tethering to mitochondria and peroxisomes then coordinates MAVS localization to form a signaling synapse between membranes. Importantly, the hepatitis C virus NS3/4A protease, which cleaves MAVS to support persistent infection, targets this synapse for MAVS proteolysis from the MAM, but not from mitochondria, to ablate RIG-I signaling of immune defenses. Thus, the MAM mediates an intracellular immune synapse that directs antiviral innate immunity.

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Published In

Proc Natl Acad Sci U S A

DOI

EISSN

1091-6490

Publication Date

August 30, 2011

Volume

108

Issue

35

Start / End Page

14590 / 14595

Location

United States

Related Subject Headings

  • Viral Nonstructural Proteins
  • Receptors, Immunologic
  • Mitochondria
  • Intracellular Membranes
  • Immunological Synapses
  • Immunity, Innate
  • Humans
  • Hepacivirus
  • Endoplasmic Reticulum
  • DEAD-box RNA Helicases
 

Citation

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Horner, S. M., Liu, H. M., Park, H. S., Briley, J., & Gale, M. (2011). Mitochondrial-associated endoplasmic reticulum membranes (MAM) form innate immune synapses and are targeted by hepatitis C virus. Proc Natl Acad Sci U S A, 108(35), 14590–14595. https://doi.org/10.1073/pnas.1110133108
Horner, Stacy M., Helene Minyi Liu, Hae Soo Park, Jessica Briley, and Michael Gale. “Mitochondrial-associated endoplasmic reticulum membranes (MAM) form innate immune synapses and are targeted by hepatitis C virus.Proc Natl Acad Sci U S A 108, no. 35 (August 30, 2011): 14590–95. https://doi.org/10.1073/pnas.1110133108.
Horner SM, Liu HM, Park HS, Briley J, Gale M. Mitochondrial-associated endoplasmic reticulum membranes (MAM) form innate immune synapses and are targeted by hepatitis C virus. Proc Natl Acad Sci U S A. 2011 Aug 30;108(35):14590–5.
Horner, Stacy M., et al. “Mitochondrial-associated endoplasmic reticulum membranes (MAM) form innate immune synapses and are targeted by hepatitis C virus.Proc Natl Acad Sci U S A, vol. 108, no. 35, Aug. 2011, pp. 14590–95. Pubmed, doi:10.1073/pnas.1110133108.
Horner SM, Liu HM, Park HS, Briley J, Gale M. Mitochondrial-associated endoplasmic reticulum membranes (MAM) form innate immune synapses and are targeted by hepatitis C virus. Proc Natl Acad Sci U S A. 2011 Aug 30;108(35):14590–14595.
Journal cover image

Published In

Proc Natl Acad Sci U S A

DOI

EISSN

1091-6490

Publication Date

August 30, 2011

Volume

108

Issue

35

Start / End Page

14590 / 14595

Location

United States

Related Subject Headings

  • Viral Nonstructural Proteins
  • Receptors, Immunologic
  • Mitochondria
  • Intracellular Membranes
  • Immunological Synapses
  • Immunity, Innate
  • Humans
  • Hepacivirus
  • Endoplasmic Reticulum
  • DEAD-box RNA Helicases