Chaperone-mediated coupling of endoplasmic reticulum and mitochondrial Ca2+ channels
By G. Szabadkai, K. Bianchi, P. Várnai, Diego De Stefani, M. Wieckowski, Dario Cavagna, Anikó Nagy, T. Balla, R. Rizzuto. Journal of Cell Biology, 2006
1,365 citations recorded by the source corpus.
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.
Subfields: Cell Biology, Molecular Biology
View Paper: https://www.semanticscholar.org/paper/b809ea83bccc19e3a0e38bfbc419256d6a3e5fd9
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Citations in the corpus
- Imaging interorganelle contacts and local calcium dynamics at the ER-mitochondrial interface (2010, neutral): “…lengths and seem to include the Mmm1/Mdm10/Mdm12/Mdm34 complex in yeast (Kornmann et al., 2009) and IP3 receptor (IP3R)-containing complexes (Szabadkai et al., 2006), Mfn2 (de Brito and Scorrano, 2008), and several other proteins (Csordás et al., 2006; Merk- wirth and Langer, 2008) in…”
- Sigma-1 receptor chaperones at the ER-mitochondrion interface regulate Ca(2+) signaling and cell survival. (2007, neutral): “A very recent study found that the mitochondrial chaperone grp75 also regulates IP3R-mediated mitochondrial Ca2+ signaling ( Szabadkai et al., 2006 ).”
- Upregulated function of mitochondria-associated ER membranes in Alzheimer disease (2012, neutral): “We used antibodies to PS1 (aa 1–65 (Calbiochem 529591) and aa 303– 316 (Calbiochem PC267)), PEMT (a gift of Joan Vance, University of Alberta), VDAC1 (Abcam ab15895), ACAT1 (Abcam ab39327), Na þ /K þ -ATPase (Abcam ab7671), SRC tyrosine kinase (Abcam ab32102), NDUFA9 (monoclonal; Molecular Probes A2”
- Ca2+ signalling checkpoints in cancer: remodelling Ca2+ for cancer cell proliferation and survival (2008, background): “Fourth, InsP 3 Rs have been localized to sites of ER–mitochondrial interaction (mitochondrial associated ER membranes) where their activity is regulated by chaperoning through the activity of SIGMA receptors and GRP75 (also known as HSPA9”
- Isolation of mitochondria-associated membranes and mitochondria from animal tissues and cells (2009, background): “and interaction with the outer mitochondrial membrane (OMM) resident voltage-dependent anion channel (VDAC) have been recently prove”
- Calcium and apoptosis: ER-mitochondria Ca2+ transfer in the control of apoptosis (2008, background): “In a recent study, we found that the mitochondrial chaperone grp75 regulates IP3R-mediated mitochondrial Ca2þ signaling (Szabadkai et al., 2006).”