Modulation of Ca(2+) Signaling by Anti-apoptotic B-Cell Lymphoma 2 Proteins at the Endoplasmic Reticulum-Mitochondrial Interface
Abstract
Mitochondria are important regulators of cell death and cell survival. Mitochondrial Ca(2+) levels are critically involved in both of these processes. On the one hand, excessive mitochondrial Ca(2+) leads to Ca(2+)-induced mitochondrial outer membrane permeabilization and thus apoptosis. On the other hand, mitochondria need Ca(2+) in order to efficiently fuel the tricarboxylic acid cycle and maintain adequate mitochondrial bioenergetics. For obtaining this Ca(2+), the mitochondria are largely dependent on close contact sites with the endoplasmic reticulum (ER), the so-called mitochondria-associated ER membranes. There, the inositol 1,4,5-trisphosphate receptors are responsible for the Ca(2+) release from the ER. It comes as no surprise that this Ca(2+) release from the ER and the subsequent Ca(2+) uptake at the mitochondria are finely regulated. Cancer cells often modulate ER-Ca(2+) transfer to the mitochondria in order to promote cell survival and to inhibit cell death. Important regulators of these Ca(2+) signals and the onset of cancer are the B-cell lymphoma 2 (Bcl-2) family of proteins. An increasing number of reports highlight the ability of these Bcl-2-protein family members to finely regulate Ca(2+) transfer from ER to ...Continue Reading
References
Targeting Bcl-2-IP3 receptor interaction to reverse Bcl-2's inhibition of apoptotic calcium signals.
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