Mitochondrial AKAP121 links cAMP and src signaling to oxidative metabolism.
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.
Livigni
Alessandra
A
Dipartimento di Biologia e Patologia Molecolare e Cellulare, Istituto di Endocrinologia ed Oncologia Sperimentale, CNR, 80131 Napoli, Italy.
Scorziello
Antonella
A
Agnese
Savina
S
Adornetto
Annagrazia
A
Carlucci
Annalisa
A
Garbi
Corrado
C
Castaldo
Imma
I
Annunziato
Lucio
L
Avvedimento
Enrico V
EV
Feliciello
Antonio
A
D054758:A Kinase Anchor Proteins; D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000255:Adenosine Triphosphate / Q000096:biosynthesis; D000818:Animals; D002460:Cell Line; D000242:Cyclic AMP / Q000378:metabolism*; D004789:Enzyme Activation; D006801:Humans; D008564:Membrane Potentials; D051379:Mice; D008928:Mitochondria / Q000378:metabolism*; D016877:Oxidants / Q000378:metabolism*; D010084:Oxidation-Reduction; D010766:Phosphorylation; D011485:Protein Binding; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism; D015398:Signal Transduction; D013379:Substrate Specificity; D019061:src-Family Kinases / Q000235:genetics / Q000378:metabolism*
D054758:A Kinase Anchor Proteins; D048868:Adaptor Proteins, Signal Transducing; C486333:Akap1 protein, mouse; D016877:Oxidants; D000255:Adenosine Triphosphate; D000242:Cyclic AMP; D019061:src-Family Kinases; D017027:Protein Tyrosine Phosphatases