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Toll-like receptors hit calcium

Marina de Bernard1, Rosario Rizzuto

  • 1Department of Biology, University of Padova, Padova, Italy.

EMBO Reports
|April 3, 2014
PubMed

Insights

Toll-like receptor 9 (TLR9) activation by CpG oligodeoxynucleotides inhibits mitochondrial calcium uptake and aerobic metabolism. This newly identified pathway links TLR signaling to mitochondrial function, impacting cellular energy production.

Area of Science:

  • Cellular Biology
  • Immunology
  • Mitochondrial Research

Background:

  • Mitochondrial calcium (Ca2+) uptake regulates metabolic enzymes and cell death pathways.
  • Released mitochondrial DNA acts as a damage-associated molecular pattern (DAMP), initiating inflammatory responses.
  • Toll-like receptors (TLRs) are crucial in innate immunity and can influence cellular processes.

Purpose of the Study:

  • To elucidate the mechanism by which Toll-like receptors (TLRs) modulate mitochondrial activity.
  • To identify a novel TLR signal transduction pathway impacting mitochondrial function.

Main Methods:

  • Investigated the interaction between TLR9 signaling and mitochondrial calcium uptake.
  • Examined the effect of CpG oligodeoxynucleotide stimulation on SERCA2 activity and mitochondrial function in non-immune cells.

Main Results:

  • TLR9 activation by CpG oligodeoxynucleotides leads to the inhibition of SERCA2.
  • This inhibition reduces calcium transfer to mitochondria, consequently decreasing aerobic metabolism.
  • A novel TLR9-SERCA2-mitochondria axis was identified.

Conclusions:

  • TLR9 signaling directly impacts mitochondrial function by regulating calcium influx.
  • This finding establishes a feedback loop where TLR activation influences mitochondrial activity, connecting innate immunity and cellular metabolism.

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