Control of calcium signal propagation to the mitochondria by inositol 1,4,5-trisphosphate-binding proteins

Xuena Lin, P. Várnai, György Csordás, A. Balla, Takeharu Nagai, Atsushi Miyawaki, Tamás Balla, György Hajnóczky

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

Cytosolic Ca2+ ([Ca2+]c) signals triggered by many agonists are established through the inositol 1,4,5-trisphosphate (IP3) messenger pathway. This pathway is believed to use Ca 2+-dependent local interactions among IP3 receptors (IP3R) and other Ca2+ channels leading to coordinated Ca2+ release from the endoplasmic reticulum throughout the cell and coupling Ca 2+ entry and mitochondrial Ca2+ uptake to Ca2+ release. To evaluate the role of IP3 in the local control mechanisms that support the propagation of [Ca2+]c waves, store-operated Ca2+ entry, and mitochondrial Ca2+ uptake, we used two IP3-binding proteins (IP3BP): 1) the PH domain of the phospholipase C-like protein, p130 (p130PH); and 2) the ligand-binding domain of the human type-I IP3R (IP3R224-605). As expected, p130PH-GFP and GFP-IP3R224-605 behave as effective mobile cytosolic IP3 buffers. In COS-7 cells, the expression of IP3BPs had no effect on store-operated Ca2+ entry. However, the IP 3-linked [Ca2+]c signal appeared as a regenerative wave and IP3BPs slowed down the wave propagation. Most importantly, IP3BPs largely inhibited the mitochondrial [Ca2+] signal and decreased the relationship between the [Ca2+]c and mitochondrial [Ca2+] signals, indicating disconnection of the mitochondria from the [Ca2+]c signal. These data suggest that IP3 elevations are important to regulate the local interactions among IP3Rs during propagation of [Ca2+]c waves and that the IP3-dependent synchronization of Ca2+ release events is crucial for the coupling between Ca2+ release and mitochondrial Ca2+ uptake.

Original languageEnglish
Pages (from-to)12820-12832
Number of pages13
JournalJournal of Biological Chemistry
Volume280
Issue number13
DOIs
Publication statusPublished - Apr 1 2005

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Inositol 1,4,5-Trisphosphate Receptors
Mitochondria
Inositol 1,4,5-Trisphosphate
Carrier Proteins
Calcium
COS Cells
Type C Phospholipases
Endoplasmic Reticulum
Buffers
Ligands
Wave propagation
Synchronization
Proteins
Pleckstrin Homology Domains

ASJC Scopus subject areas

  • Biochemistry

Cite this

Control of calcium signal propagation to the mitochondria by inositol 1,4,5-trisphosphate-binding proteins. / Lin, Xuena; Várnai, P.; Csordás, György; Balla, A.; Nagai, Takeharu; Miyawaki, Atsushi; Balla, Tamás; Hajnóczky, György.

In: Journal of Biological Chemistry, Vol. 280, No. 13, 01.04.2005, p. 12820-12832.

Research output: Contribution to journalArticle

Lin, Xuena ; Várnai, P. ; Csordás, György ; Balla, A. ; Nagai, Takeharu ; Miyawaki, Atsushi ; Balla, Tamás ; Hajnóczky, György. / Control of calcium signal propagation to the mitochondria by inositol 1,4,5-trisphosphate-binding proteins. In: Journal of Biological Chemistry. 2005 ; Vol. 280, No. 13. pp. 12820-12832.
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