A phosphodiesterase 2A isoform localized to mitochondria regulates respiration.
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Acin-Perez R, Russwurm M, Gunnewig K, Gertz M, Zoidl G, Ramos L, Buck J, Levin LR, Rassow J, Manfredi G, Steegborn C
A phosphodiesterase 2A isoform localized to mitochondria regulates respiration.
J Biol Chem. 2011 Sep 2;286(35):30423-32. doi: 10.1074/jbc.M111.266379. Epub 2011 Jul 1.
- PubMed ID
- 21724846 [ View in PubMed]
- Abstract
Mitochondria are central organelles in cellular energy metabolism, apoptosis, and aging processes. A signaling network regulating these functions was recently shown to include soluble adenylyl cyclase as a local source of the second messenger cAMP in the mitochondrial matrix. However, a mitochondrial cAMP-degrading phosphodiesterase (PDE) necessary for switching off this cAMP signal has not yet been identified. Here, we describe the identification and characterization of a PDE2A isoform in mitochondria from rodent liver and brain. We find that mitochondrial PDE2A is located in the matrix and that the unique N terminus of PDE2A isoform 2 specifically leads to mitochondrial localization of this isoform. Functional assays show that mitochondrial PDE2A forms a local signaling system with soluble adenylyl cyclase in the matrix, which regulates the activity of the respiratory chain. Our findings complete a cAMP signaling cascade in mitochondria and have implications for understanding the regulation of mitochondrial processes and for their pharmacological modulation.