Chaperone-mediated coupling of endoplasmic reticulum and mitochondrial Ca2+ channels

György Szabadkai, Katiuscia Bianchi, Péter Várnai, Diego De Stefani, Mariusz R. Wieckowski, Dario Cavagna, Anikó I. Nagy, Tamás Balla, Rosario Rizzuto

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The voltage-dependent anion channel (VDAC) of the outer mitochondrial membrane mediates metabolic flow, Ca2+, and cell death signaling between the endoplasmic reticulum (ER) and mitochondrial networks. We demonstrate that VDAC1 is physically linked to the endoplasmic reticulum Ca 2+-release channel inositol 1,4,5-trisphosphate receptor (IP 3R) through the molecular chaperone glucose-regulated protein 75 (grp75). Functional interaction between the channels was shown by the recombinant expression of the ligand-binding domain of the IP3R on the ER or mitochondrial surface, which directly enhanced Ca2+ accumulation in mitochondria. Knockdown of grp75 abolished the stimulatory effect, highlighting chaperone-mediated conformational coupling between the IP3R and the mitochondrial Ca2+ uptake machinery. Because organelle Ca 2+ homeostasis influences fundamentally cellular functions and death signaling, the central location of grp75 may represent an important control point of cell fate and pathogenesis.

Original languageEnglish
Pages (from-to)901-911
Number of pages11
JournalJournal of Cell Biology
Issue number6
Publication statusPublished - Dec 18 2006


ASJC Scopus subject areas

  • Cell Biology

Cite this

Szabadkai, G., Bianchi, K., Várnai, P., De Stefani, D., Wieckowski, M. R., Cavagna, D., Nagy, A. I., Balla, T., & Rizzuto, R. (2006). Chaperone-mediated coupling of endoplasmic reticulum and mitochondrial Ca2+ channels. Journal of Cell Biology, 175(6), 901-911.