TY - JOUR
T1 - Mitochondrial AKAP121 links cAMP and src signaling to oxidative metabolism
AU - Livigni, Alessandra
AU - Scorziello, Antonella
AU - Agnese, Savina
AU - Adornetto, Annagrazia
AU - Carlucci, Annalisa
AU - Garbi, Corrado
AU - Castaldo, Imma
AU - Annunziato, Lucio
AU - Avvedimento, Enrico V.
AU - Feliciello, Antonio
PY - 2006/1
Y1 - 2006/1
N2 - 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.
AB - 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.
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UR - http://www.scopus.com/inward/citedby.url?scp=30044434361&partnerID=8YFLogxK
U2 - 10.1091/mbc.E05-09-0827
DO - 10.1091/mbc.E05-09-0827
M3 - Article
C2 - 16251349
AN - SCOPUS:30044434361
VL - 17
SP - 263
EP - 271
JO - Molecular Biology of the Cell
JF - Molecular Biology of the Cell
SN - 1059-1524
IS - 1
ER -