Fig. 3. The role of calcium ions in communicating death signals to mitochondria, and its regulation by Bcl-2. The ER lumen serves as a source of calcium ions that are released via InsP₃ receptors. The resulting elevation of cytosolic calcium either directly mediates loss of mitochondrial permeability transition through increased uptake of calcium into the mitochondrial matrix, a process that is enhanced by permeabilization of the outer mitochondrial membrane by tcBid, or indirectly by activating calcineurin, which in turn activates Bad. Bcl-2 located on the ER membrane interferes with calcium-mediated apoptotic signals, either by decreasing ER lumenal calcium concentration (left) or by docking calcineurin to InsP3 receptors, thereby inhibiting InsP3-mediated calcium release and calcineurin-mediated dephosphorylation of Bad-P (right).

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