3 research outputs found
Chaperone-mediated coupling of endoplasmic reticulum and mitochondrial Ca2+ channels
open9siThe voltage-dependent anion channel (VDAC) of the outer mitochondrial membrane mediates metabolic flow, Ca(2+), 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(3)R) 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 IP(3)R on the ER or mitochondrial surface, which directly enhanced Ca(2+) accumulation in mitochondria. Knockdown of grp75 abolished the stimulatory effect, highlighting chaperone-mediated conformational coupling between the IP(3)R and the mitochondrial Ca(2+) 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.openSzabadkai G.; Bianchi K.; Várnai P.; De Stefani D.; Wieckowski M.R.; Cavagna D.; Nagy A.I.; Balla T.; Rizzuto R.Szabadkai, Gyorgy; Bianchi, Katiuscia; Várnai, P.; DE STEFANI, Diego; Wieckowski, Mariusz; Cavagna, Dario; Nagy, A. I.; Balla, T.; Rizzuto, Rosari