Mitochondrion: an emerging platform critical for host antiviral signaling

Expert Opin Ther Targets. 2011 May;15(5):647-65. doi: 10.1517/14728222.2011.561321. Epub 2011 Feb 26.


Introduction: Toll-like receptors (TLRs) and cytoplasmic retinoic acid-inducible gene I (RIG-I)-like receptors (RLRs) are the two major receptor systems for detecting RNA viruses. RLRs play essential roles within the cytosol of various cell types. The signaling pathways converge at the mitochondrial antiviral signalling protein (MAVS) on the outer membrane of mitochondria. Recent research has surprisingly shown that many mitochondrial intrinsic factors play novel functions in RLR signaling, conferring a new perspective of therapeutic drug design to inhibit viral infection.

Areas covered: This review covers the literature of the past 6 years and summarizes the components, regulation and mechanisms of RLR signaling, highlighting the function and regulation of mitochondrial proteins, such as MAVS and translocase of outer membrane (Tom)70 in this process. The authors attempt to delineate the complicated cross-talk among subcellular organelles in the context of intracellular antiviral signaling.

Expert opinion: It is imperative to elucidate the specific roles and mechanisms of post-translational modifications in MAVS signaling. The sub-cellular dynamics of regulatory proteins should be correlated with their multiple functions. Animal models are needed to further probe the integration of mitochondria with innate immunity evolutionarily; they will be instrumental for identifying novel antiviral targets and, ultimately, for developing specific clinical drugs.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • DEAD Box Protein 58
  • DEAD-box RNA Helicases / physiology
  • Humans
  • Immunity, Innate*
  • Interferon-Induced Helicase, IFIH1
  • Mitochondrial Proteins / physiology*
  • NF-kappa B / physiology
  • Protein Processing, Post-Translational
  • Signal Transduction*
  • Virus Diseases / immunology*


  • Mitochondrial Proteins
  • NF-kappa B
  • DDX58 protein, human
  • IFIH1 protein, human
  • DEAD Box Protein 58
  • DEAD-box RNA Helicases
  • Interferon-Induced Helicase, IFIH1