Inositol 1,4, 5-trisphosphate receptor/GAPDH complex augments Ca2+ release via locally derived NADH.

NADH regulates the release of calcium from the endoplasmic reticulum by modulation of inositol 1,4,5-trisphosphate receptors (IP₃R), accounting for the augmented calcium release of hypoxic cells. We report selective binding of IP₃R to GAPDH, whose activity leads to the local generation of NADH to regulate intracellular calcium signaling. This interaction requires cysteines 992 and 995 of IP₃R and C150 of GAPDH. Addition of native GAPDH and NAD⁺ to WT IP₃R stimulates calcium release, whereas no stimulation occurs with C992S/995S IP₃R that cannot bind GAPDH. Thus, the IP₃R/ GAPDH interaction likely enables cellular energy dynamics to impact calcium signaling. [ABSTRACT FROM AUTHOR]