Mitochondrial AKAP121 links cAMP and src signaling to oxidative metabolism

Alessandra Livigni, Antonella Scorziello, Savina Agnese, Annagrazia Adornetto, Annalisa Carlucci, Corrado Garbi, Imma Castaldo, Lucio Annunziato, Enrico V. Avvedimento, Antonio Feliciello

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Abstract

AKAP121 focuses distinct signaling events from membrane to mitochondria by binding and targeting cAMP-dependent protein kinase (PKA), protein tyrosine phosphatase (PTPD1), and mRNA. We find that AKAP121 also targets src tyrosine kinase to mitochondria via PTPD1. AKAP121 increased src-dependent phosphorylation of mitochondrial substrates and enhanced the activity of cytochrome c oxidase, a component of the mitochondrial respiratory chain. Mitochondrial membrane potential and ATP oxidative synthesis were enhanced by AKAP121 in an src- and PKA-dependent manner. Finally, siRNA-mediated silencing of endogenous AKAP121 drastically impaired synthesis and accumulation of mitochondrial ATP. These findings indicate that AKAP121, through its role in enhancing cAMP and tyrosine kinase signaling to distal organelles, is an important regulator in mitochondrial metabolism.

Original languageEnglish
Pages (from-to)263-271
Number of pages9
JournalMolecular Biology of the Cell
Volume17
Issue number1
DOIs
Publication statusPublished - Jan 2006

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ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cell Biology

Cite this

Livigni, A., Scorziello, A., Agnese, S., Adornetto, A., Carlucci, A., Garbi, C., Castaldo, I., Annunziato, L., Avvedimento, E. V., & Feliciello, A. (2006). Mitochondrial AKAP121 links cAMP and src signaling to oxidative metabolism. Molecular Biology of the Cell, 17(1), 263-271. https://doi.org/10.1091/mbc.E05-09-0827