title: The cAMP phosphodiesterase Prune localizes to the mitochondrial matrix and promotes mtDNA replication by stabilizing TFAM.
abstract: Compartmentalized cAMP signaling regulates mitochondrial dynamics, morphology, and oxidative phosphorylation. However, regulators of the mitochondrial cAMP pathway, and its broad impact on organelle function, remain to be explored. Here, we report that Drosophila Prune is a cyclic nucleotide phosphodiesterase that localizes to the mitochondrial matrix. Knocking down prune in cultured cells reduces mitochondrial transcription factor A (TFAM) and mitochondrial DNA (mtDNA) levels. Our data suggest that Prune stabilizes TFAM and promotes mitochondrial DNA (mtDNA) replication through downregulation of mitochondrial cAMP signaling. In addition, our work demonstrates the prevalence of mitochondrial cAMP signaling in metazoan and its new role in mitochondrial biogenesis.
authors: Laboratory of Molecular Genetics, National Heart, Lung and Blood Institute, Bethesda, MD, USA.
authors: Fan
authors: F
authors: Zhang
authors: Laboratory of Molecular Genetics, National Heart, Lung and Blood Institute, Bethesda, MD, USA.
authors: Yun
authors: Y
authors: Qi
authors: Laboratory of Molecular Genetics, National Heart, Lung and Blood Institute, Bethesda, MD, USA.
authors: Kiet
authors: K
authors: Zhou
authors: National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, MD, USA.
authors: Guofeng
authors: G
authors: Zhang
authors: Laboratory of Molecular Genetics, National Heart, Lung and Blood Institute, Bethesda, MD, USA.
authors: Kaari
authors: K
authors: Linask
authors: Laboratory of Molecular Genetics, National Heart, Lung and Blood Institute, Bethesda, MD, USA hong.xu@nih.gov.
authors: Hong
authors: H
authors: Xu
mesh_terms: D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism; D004261:DNA Replication; D004272:DNA, Mitochondrial / Q000235:genetics* / Q000378:metabolism; D029721:Drosophila Proteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D004331:Drosophila melanogaster / Q000201:enzymology / Q000235:genetics*; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D008928:Mitochondria / Q000201:enzymology / Q000235:genetics* / Q000648:ultrastructure; D001678:Organelle Biogenesis; D010085:Oxidative Phosphorylation; D055550:Protein Stability; D012330:RNA, Double-Stranded / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D000097573:Red Fluorescent Protein
chemical_list: D015105:3',5'-Cyclic-AMP Phosphodiesterases; D000242:Cyclic AMP; D004272:DNA, Mitochondrial; D029721:Drosophila Proteins; D049452:Green Fluorescent Proteins; D008164:Luminescent Proteins; D012330:RNA, Double-Stranded; D014157:Transcription Factors; D000097573:Red Fluorescent Protein; C070996:PN protein, Drosophila; C489029:TFAM protein, Drosophila
keywords: cyclic adenosine 3′,5′‐monophosphate; cyclic nucleotide phosphodiesterase; mitochondrial DNA; mitochondrial transcription factor A; neurodegeneration
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