title: Toll-like receptors hit calcium.
abstract: Mitochondrial Ca(2+) uptake is a multifarious signal that controls both the activity of matrix dehydrogenases and the sensitivity to apoptotic and necrotic challenges. Recent evidence indicates that mitochondria also play a role in triggering inflammation, as mitochondrial DNA, when released by the cell, is an important damage-associated molecular pattern (DAMP). Now, Toll-like receptors (TLRs) are shown to close the loop, by affecting in turn mitochondrial activity. Two studies by Shintani and colleagues, one in this issue of EMBO reports, identify a new TLR transduction mechanism that impinges directly on mitochondrial function. Upon binding of CpG oligodeoxynucleotides, TLR9--which in non-immune cells is retained in the ER--inhibits SERCA2, thus reducing Ca(2+) transfer to the mitochondria and aerobic metabolism.
authors.affiliation: Department of Biology, University of Padova, Padova, Italy.
authors.forename: Marina
authors.initials: M
authors.lastname: de Bernard
authors.forename: Rosario
authors.initials: R
authors.lastname: Rizzuto
mesh_terms: D001693:Biological Transport, Active; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling; D004721:Endoplasmic Reticulum / Q000276:immunology; D006801:Humans; D007249:Inflammation / Q000276:immunology; D015850:Interleukin-6 / Q000276:immunology; D008928:Mitochondria / Q000378:metabolism*; D016328:NF-kappa B / Q000037:antagonists & inhibitors; D009838:Oligodeoxyribonucleotides; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000037:antagonists & inhibitors; D051217:Toll-Like Receptor 9 / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
chemical_list: C408982:CPG-oligonucleotide; C508600:IL6 protein, human; D015850:Interleukin-6; D016328:NF-kappa B; D009838:Oligodeoxyribonucleotides; C495371:TLR9 protein, human; D051217:Toll-Like Receptor 9; D014409:Tumor Necrosis Factor-alpha; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; C506946:ATP2A2 protein, human; D002118:Calcium