Abstract：
: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.
journal_name
J Cell Scijournal_title
Journal of cell scienceauthors
Scorziello A,Savoia C,Sisalli MJ,Adornetto A,Secondo A,Boscia F,Esposito A,Polishchuk EV,Polishchuk RS,Molinaro P,Carlucci A,Lignitto L,Di Renzo G,Feliciello A,Annunziato Ldoi
10.1242/jcs.129668subject
Has Abstractpub_date
2013-12-15 00:00:00pages
5566-77issue
Pt 24eissn
0021-9533issn
1477-9137pii
jcs.129668journal_volume
126pub_type
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