Figure 3.

Regulation of VDAC by subcellular localization. A fraction of VDAC channels was shown to be present in couplons with Ca²⁺ release channels of the ER/SR, in particular VDAC1 with the IP3R or VDAC2 with the RyR. These couplons represent hotspots of Ca²⁺-mediated regulation of mitochondrial activity. In addition to the strategic positioning of VDAC in close vicinity to the mouth of the release channels, other factors might regulate VDAC within and outside the couplons for the specialized tasks within these environments. These include isoform selectivity, protein partners, the lipidic environment, and the voltage-gated state of the channel. Depending on the VDAC localization, these factors might determine whether VDAC serves as a Ca²⁺ or metabolite channel.