Capture at the ER-mitochondrial contacts licenses IP 3 receptors to stimulate local Ca 2+ transfer and oxidative metabolism

• Published in: Nature communications 2022-11, Vol.13 (1), p.6779
• Main Authors: Katona, Máté, Bartók, Ádám, Nichtova, Zuzana, Csordás, György, Berezhnaya, Elena, Weaver, David, Ghosh, Arijita, Várnai, Péter, Yule, David I, Hajnóczky, György
• Format: Article
• Language: English
• Subjects: Calcium - metabolism; Calcium Signaling - physiology; Cell Respiration; Inositol 1,4,5-Trisphosphate Receptors - metabolism; Mitochondria - metabolism; Oxidative Stress
• ISSN: 2041-1723
• DOI: 10.1038/s41467-022-34365-8

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 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 coupling, IP3Rs captured at mitochondria promptly mediate Ca transfer, stimulating mitochondrial oxidative metabolism. The Ca 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.