Essential role of A-Kinase anchor protein 121 for cAMP signaling to mitochondria

Adele Affaitati, Luca Cardone, Tiziana De Cristofaro, Annalisa Carlucci, Michael D. Ginsberg, Stelio Varrone, Max E. Gottesman, Enrico V. Avvedimento, Antonio Feliciello

Research output: Contribution to journalArticle

Abstract

A-Kinase anchor proteins (AKAPs) immobilize and concentrate protein kinase A (PKA) isoforms at specific subcellular compartments. Intracellular targeting of PKA holoenzyme elicits rapid and efficient phosphorylation of target proteins, thereby increasing sensitivity of downstream effectors to cAMP action. AKAP121 targets PKA to the cytoplasmic surface of mitochondria. Here we show that conditional expression of AKAP121 in PC12 cells selectively enhances cAMP·PKA signaling to mitochondria. AKAP121 induction stimulates PKA-dependent phosphorylation of the proapoptotic protein BAD at Ser 155, inhibits release of cytochrome c from mitochondria, and protects cells from apoptosis. An AKAP121 derivative mutant that localizes on mitochondria but does not bind PKA down-regulates PKA signaling to the mitochondria and promotes apoptosis. These findings indicate that PKA anchored by AKAP121 transduces cAMP signals to the mitochondria, and it may play an important role in mitochondrial physiology.

Original languageEnglish
Pages (from-to)4286-4294
Number of pages9
JournalJournal of Biological Chemistry
Volume278
Issue number6
DOIs
Publication statusPublished - Feb 7 2003

ASJC Scopus subject areas

  • Biochemistry

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    Affaitati, A., Cardone, L., De Cristofaro, T., Carlucci, A., Ginsberg, M. D., Varrone, S., Gottesman, M. E., Avvedimento, E. V., & Feliciello, A. (2003). Essential role of A-Kinase anchor protein 121 for cAMP signaling to mitochondria. Journal of Biological Chemistry, 278(6), 4286-4294. https://doi.org/10.1074/jbc.M209941200