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- Title
Chaperone-mediated coupling of endoplasmic reticulum and mitochondrial Ca2+ channels.
- Authors
Szabadkai, György; Bianchi, Katiuscia; Várnai, Péter; De Stefani, Diego; Wieckowski, Mariusz R; Cavagna, Dario; Nagy, Anikó I; Balla, Tamás; Rizzuto, Rosario
- Abstract
The 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.
- Publication
The Journal of cell biology, 2006, Vol 175, Issue 6, p901
- ISSN
0021-9525
- Publication type
Journal Article
- DOI
10.1083/jcb.200608073