Editors' ChoiceCalcium

Linking Store-Operated Calcium Channels to Mitochondria

Science's STKE  07 Jan 2003:
Vol. 2003, Issue 164, pp. tw2-TW2
DOI: 10.1126/stke.2003.164.tw2

Changes in the concentration of cytosolic calcium underlie many cellular processes. Calcium can come from outside the cell through plasma membrane channels or from inside the cell from intracellular stores, such as the endoplasmic reticulum (ER). When the intracellular stores are depleted, a signal is generated that stimulates a calcium current known as ICRAC. Glitsch et al. depolarized mitochondria before or after depleting the ER store with either the calcium pump inhibitor thapsigargin or by activation of inositol trisphosphate receptors (IP3Rs) in weak calcium buffer. When the mitochondria were depolarized, ICRAC was decreased compared with conditions with normal respiring mitochondria. Various electrophysiological experiments in the presence of pharmacological agents suggested that this effect was not due to calcium-dependent fast inactivation of the ICRAC channel, inhibition of depletion of the stores, depletion of intracellular adenosine triphosphate (ATP), or opening of the permeability transition pore of the mitochondria. Depolarization of the mitochondria reduces the driving force for calcium uptake by the mitochondria, which suggests that there may be a calcium-dependent mitochondrial component to the stimulation of the store-operated channel. Indeed, ruthenium red, which inhibits the mitochondrial calcium uniporter, among other targets, decreased ICRAC. The authors suggest that the mitochondria may release a factor in response to calcium uptake under conditions where there is weak cytosolic calcium buffering, which in turn leads to the enhancement of store-operated calcium entry.

M. D. Glitsch, D. Bakowski, A. B. Parekh, Store-operated Ca2+ entry depends on mitochondrial Ca2+ uptake. EMBO J. 21, 6744-6754 (2002). [Abstract] [Full Text]