Toll-like receptors hit calcium

Mitochondrial Ca2+ 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, TLR9which in non-immune cells is retained in the ERinhibits SERCA2, thus reducing Ca2+ transfer to the mitochondria and aerobic metabolism.