Endoplasmic reticulum-mitochondria contacts (ERMCs) are restructured in response to
changes in cell state. While this restructuring has been implicated as a cause or
consequence of pathology in numerous systems, the underlying molecular dynamics are
poorly understood. Here, we show means to visualize the capture of motile IP 3 receptors
(IP3Rs) at ERMCs and document the immediate consequences for calcium signaling and
metabolism. IP3Rs are of particular interest because their presence provides a scaffold
for ERMCs that mediate local calcium signaling, and their function outside of ERMCs
depends on their motility. Unexpectedly, in a cell model with little ERMC Ca 2+ coupling,
IP3Rs captured at mitochondria promptly mediate Ca 2+ transfer, stimulating mitochondrial
oxidative metabolism. The Ca 2+ transfer does not require linkage with a pore-forming
protein in the outer mitochondrial membrane. Thus, motile IP3Rs can traffic in and
out of ERMCs, and, when ‘parked’, mediate calcium signal propagation to the mitochondria,
creating a dynamic arrangement that supports local communication.
