| First Author | Scorziello A | Year | 2013 |
| Journal | J Cell Sci | Volume | 126 |
| Issue | Pt 24 | Pages | 5566-77 |
| PubMed ID | 24101730 | Mgi Jnum | J:225481 |
| Mgi Id | MGI:5693358 | Doi | 10.1242/jcs.129668 |
| Citation | Scorziello A, et al. (2013) NCX3 regulates mitochondrial Ca(2+) handling through the AKAP121-anchored signaling complex and prevents hypoxia-induced neuronal death. J Cell Sci 126(Pt 24):5566-77 |
| abstractText | The mitochondrial influx and efflux of Ca(2+) play a relevant role in cytosolic and mitochondrial Ca(2+) homeostasis, and contribute to the regulation of mitochondrial functions in neurons. The mitochondrial Na(+)/Ca(2+) 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(+)-dependent Na(+)/Ca(2+) exchanger extruding Ca(2+) 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(2+) 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(2+) 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(2+) efflux mode at the level of the OMM. Collectively, these results suggest that, in neurons, NCX3 regulates mitochondrial Ca(2+) handling from the OMM through an AKAP121-anchored signaling complex, thus promoting cell survival during hypoxia. |
