Structural basis for a pH-sensitive calcium leak across membranes.

Cells maintain a balance between calcium in the cytosol and calcium stored in organelles—too much stored calcium kills cells. Transmembrane Bax inhibitor motif (TMBIM) proteins form channels in organelle membranes that allow calcium to leak out. Chang et al. show that this calcium leak is pH-dependent. A bacterial homolog of TMBIM proteins converts between an open channel at low pH and a closed channel at high pH. Although the channel is open at low pH, calcium leakage is low because the inside of the channel remains at a neutral pH. Thus, at physiological pH, these channels will be in equilibrium between the open and closed states, so that excess calcium can leak through. Science , this issue p. [1131][1] [1]: /lookup/doi/10.1126/science.1252043