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Updated: May 10, 2026

Identification of Intracellular Signaling Events Induced in Viable Cells by Interaction with Neighboring Cells Undergoing Apoptotic Cell Death
09:18

Identification of Intracellular Signaling Events Induced in Viable Cells by Interaction with Neighboring Cells Undergoing Apoptotic Cell Death

Published on: December 27, 2016

MAVS regulates apoptotic cell death by decreasing K48-linked ubiquitination of voltage-dependent anion channel 1

Kai Guan1, Zirui Zheng, Ting Song

  • 1State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Biotechnology, Beijing, China.

Molecular and Cellular Biology
|June 12, 2013
PubMed

Insights

Mitochondrial antiviral signaling protein (MAVS) binds voltage-dependent anion channel 1 (VDAC1) to trigger apoptosis, independent of its immune role. This discovery reveals a new pathway for controlling virus-induced cell death.

Area of Science:

  • Cell Biology
  • Immunology
  • Virology

Background:

  • The mitochondrial antiviral signaling protein (MAVS) is crucial for host defense against viral infections, primarily by inducing type I interferon.
  • MAVS has also been implicated in virus-induced apoptosis, but the underlying mechanisms remain largely unknown.

Purpose of the Study:

  • To elucidate the mechanism by which MAVS mediates apoptosis induction during viral infections.
  • To identify specific molecular interactions and pathways involved in MAVS-dependent apoptosis.

Main Methods:

  • Co-immunoprecipitation assays to detect MAVS-VDAC1 binding.
  • Caspase-3 activity assays to measure apoptosis.
  • Ubiquitination assays to assess VDAC1 protein stability.
  • Analysis of MAVS knockout mouse embryonic fibroblasts (MEFs) in response to vesicular stomatitis virus (VSV) infection.

Main Results:

  • MAVS directly binds to voltage-dependent anion channel 1 (VDAC1).
  • MAVS induces apoptosis through caspase-3 activation, a process independent of MAVS's innate immune signaling function.
  • MAVS enhances VDAC1 stability by reducing its K48-linked ubiquitination.
  • MAVS knockout MEFs exhibit decreased VDAC1 expression and a blunted apoptotic response to VSV infection.
  • VSV-induced VDAC1 upregulation is abolished in MAVS knockout MEFs.

Conclusions:

  • VDAC1 is identified as a direct target of MAVS.
  • A novel mechanism is described where MAVS controls virus-induced apoptosis by modulating VDAC1 stability and expression.
  • This finding expands our understanding of MAVS function beyond innate immunity into programmed cell death pathways.

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