期刊
JOURNAL OF BIOLOGICAL CHEMISTRY
卷 286, 期 35, 页码 30423-30432出版社
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.M111.266379
关键词
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资金
- National Institutes of Health [R01 GM088999, R01 GM62328, NS552555]
- Muscular Dystrophy Association
- United Mitochondrial Disease Foundation
- Deutsche Forschungsgemeinschaft
- Forschungsreferat Ruhr-Universitat Bochum Medizin [F630-2008]
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.
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