In:
The Journal of Cell Biology, Rockefeller University Press, Vol. 175, No. 6 ( 2006-12-18), p. 901-911
Abstract:
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 Ca2+-release channel inositol 1,4,5-trisphosphate receptor (IP3R) 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 Ca2+ homeostasis influences fundamentally cellular functions and death signaling, the central location of grp75 may represent an important control point of cell fate and pathogenesis.
Type of Medium:
Online Resource
ISSN:
1540-8140
,
0021-9525
DOI:
10.1083/jcb.200608073
Language:
English
Publisher:
Rockefeller University Press
Publication Date:
2006
detail.hit.zdb_id:
1421310-2
detail.hit.zdb_id:
218154-X
SSG:
12
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