A non-death function of the mitochondrial apoptosis apparatus in immunity

EMBO J. 2019 Jun 3;38(11):e100907. doi: 10.15252/embj.2018100907. Epub 2019 Apr 12.


Apoptosis is a frequent form of programmed cell death, but the apoptotic signaling pathway can also be engaged at a low level, in the absence of cell death. We here report that such sub-lethal engagement of mitochondrial apoptosis signaling causes the secretion of cytokines from human epithelial cells in a process controlled by the Bcl-2 family of proteins. We further show that sub-lethal signaling of the mitochondrial apoptosis pathway is initiated by infections with all tested viral, bacterial, and protozoan pathogens and causes damage to the genomic DNA. Epithelial cells infected with these pathogens secreted cytokines, and this cytokine secretion upon microbial infection was substantially reduced if mitochondrial sub-lethal apoptosis signaling was blocked. In the absence of mitochondrial pro-apoptotic signaling, the ability of epithelial cells to restrict intracellular bacterial growth was impaired. Triggering of the mitochondrial apoptosis apparatus thus not only causes apoptosis but also has an independent role in immune defense.

Keywords: apoptosis; cell‐autonomous immunity; immune recognition; infection; minority MOMP.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / physiology*
  • Cell Death / immunology
  • Cells, Cultured
  • Epithelial Cells / physiology
  • HCT116 Cells
  • HEK293 Cells
  • HeLa Cells
  • Humans
  • Immunity / physiology*
  • Mice
  • Mitochondria / physiology*
  • Proto-Oncogene Proteins c-bcl-2 / physiology
  • Serine Endopeptidases / physiology
  • Signal Transduction / physiology
  • bcl-2 Homologous Antagonist-Killer Protein / physiology
  • bcl-2-Associated X Protein / physiology


  • Proto-Oncogene Proteins c-bcl-2
  • bcl-2 Homologous Antagonist-Killer Protein
  • bcl-2-Associated X Protein
  • CTRL protein, human
  • Serine Endopeptidases