biostudies-literatureKatona MU.S. Department of Health & Human Services | NIH | National Institute of Dental and Craniofacial ResearchU.S. Department of Health & Human Services | NIH | National Institute of Dental and Craniofacial Research (NIDCR)6779https://www.ebi.ac.uk/biostudies/studies/S-EPMC9646835biostudies-literatureUnknown13(1)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 IP₃ 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 Ca²⁺ coupling, IP3Rs captured at mitochondria promptly mediate Ca²⁺ transfer, stimulating mitochondrial oxidative metabolism. The Ca²⁺ 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.Nature communicationsCapture at the ER-mitochondrial contacts licenses IP₃ receptors to stimulate local Ca²⁺ transfer and oxidative metabolism.PMC9646835DE014756Ghosh ACsordas GYule DINichtova ZBerezhnaya EWeaver DHajnoczky GKatona MBartok AVarnai PfalseCapture at the ER-mitochondrial contacts licenses IP₃ receptors to stimulate local Ca²⁺ transfer and oxidative metabolism.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 IP₃ 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 Ca²⁺ coupling, IP3Rs captured at mitochondria promptly mediate Ca²⁺ transfer, stimulating mitochondrial oxidative metabolism. The Ca²⁺ 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.2022-01-01T00:00:00Z2022 Nov2024-11-15T20:37:50.345Z2024-11-15T20:37:50.345ZS-EPMC96468353635190110.1038/s41467-022-34365-8