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NCX3 regulates mitochondrial Ca2+ handling through the AKAP121-anchored signaling complex and prevents hypoxia-induced neuronal death.
- Source :
- Journal of Cell Science; 12/15/2013, Vol. 126 Issue 24, p5566-5577, 12p
- Publication Year :
- 2013
-
Abstract
- The mitochondrial influx and efflux of Ca<superscript>2+</superscript> play a relevant role in cytosolic and mitochondrial Ca<superscript>2+</superscript> homeostasis, and contribute to the regulation of mitochondrial functions in neurons. The mitochondrial Na<superscript>+</superscript>/Ca<superscript>2+</superscript> exchanger, which was first postulated in 1974, has been primarily investigated only from a functional point of view, and its identity and localization in the mitochondria have been a matter of debate over the past three decades. Recently, a Li<superscript>+</superscript>-dependent Na<superscript>+</superscript>/Ca<superscript>2+</superscript> exchanger extruding Ca<superscript>2+</superscript> from the matrix has been found in the inner mitochondrial membrane of neuronal cells. However, evidence has been provided that the outer membrane is impermeable to Ca<superscript>2+</superscript> efflux into the cytoplasm. In this study, we demonstrate for the first time that the nuclear-encoded NCX3 isoform (1) is located on the outer mitochondrial membrane (OMM) of neurons; (2) colocalizes and immunoprecipitates with AKAP121 (also known as AKAP1), a member of the protein kinase A anchoring proteins (AKAPs) present on the outer membrane; (3) extrudes Ca<superscript>2+</superscript> from mitochondria through AKAP121 interaction in a PKA-mediated manner, both under normoxia and hypoxia; and (4) improves cell survival when it works in the Ca<superscript>2+</superscript> efflux mode at the level of theOMM. Collectively, these results suggest that, in neurons, NCX3 regulates mitochondrial Ca<superscript>2+</superscript> handling from the OMM through an AKAP121-anchored signaling complex, thus promoting cell survival during hypoxia. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 00219533
- Volume :
- 126
- Issue :
- 24
- Database :
- Complementary Index
- Journal :
- Journal of Cell Science
- Publication Type :
- Academic Journal
- Accession number :
- 93989344
- Full Text :
- https://doi.org/10.1242/jcs.129668