Plasticity of mitochondrial calcium signaling.
Evidence is emerging that a quasisynaptic local communication facilitates the calcium signaling between endoplasmic reticulum and mitochondria. However, it remains elusive whether the machinery of mitochondrial calcium signaling displays plasticity similar to the synaptic transmission. Here we studied the relationship between inositol 1,4,5-trisphosphate (IP3)-linked cytosolic [Ca2+] ([Ca2+]c) oscillations and the associated rise in mitochondrial matrix [Ca2+] ([Ca2+]m) in RBL-2H3 mast cells. We observed that the second [Ca2+]c spike is often associated with a larger rise in the [Ca2+]m than the first. It would appear that this phenomenon was not due to a change in the driving force for Ca2+ uptake and therefore must be due to an enhanced Ca2+ permeability of the mitochondrial Ca2+ uptake sites (uniporter). To investigate the activation and deactivation kinetics of the uniporter during IP3 receptor-mediated Ca2+ mobilization, we established novel methods. Using these approaches, we demonstrated that the IP3-induced increase in the permeability of the uniporter lasted longer than the Ca2+ signal. The sustained increase in Ca2+ permeability was bidirectional. Furthermore, the addition of Ca2+ during the decay of the IP3 effect evoked a large further increase in the uniporter permeability. Calmodulin inhibitors did not interfere with the IP3-induced initial activation of the uniporter but inhibited the sustained phase. These results suggest that the uniporter displays a calmodulin-mediated facilitation. This plasticity may allow cooperation among sequential IP3 receptor-mediated [Ca2+] transients in the control of calcium signal propagation to the mitochondria.
Csordás
György
G
Department of Pathology, Anatomy, and Cell Biology, Thomas Jefferson University, Philadelphia, PA 19107, USA.
Hajnóczky
György
G
D000818:Animals; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling; D045744:Cell Line, Tumor; D003600:Cytosol / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000378:metabolism / Q000502:physiology; D005470:Fluorometry; D015544:Inositol 1,4,5-Trisphosphate / Q000494:pharmacology; D017136:Ion Transport; D007700:Kinetics; D008407:Mast Cells; D008928:Mitochondria / Q000378:metabolism / Q000502:physiology*; D051381:Rats
D015544:Inositol 1,4,5-Trisphosphate; D002118:Calcium