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.
Keywords:
cyclic adenosine 3′,5′‐monophosphate; cyclic nucleotide phosphodiesterase; mitochondrial DNA; mitochondrial transcription factor A; neurodegeneration.
Published 2015. This article is a U.S. Government work and is in the public domain in the USA. Published under the terms of the CC BY NC ND 4.0 license.
Publication types
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Research Support, N.I.H., Intramural
MeSH terms
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3',5'-Cyclic-AMP Phosphodiesterases / genetics*
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3',5'-Cyclic-AMP Phosphodiesterases / metabolism
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Animals
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Cells, Cultured
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Cyclic AMP / metabolism
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DNA Replication*
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DNA, Mitochondrial / genetics*
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DNA, Mitochondrial / metabolism
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Drosophila Proteins / antagonists & inhibitors
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Drosophila Proteins / genetics*
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Drosophila Proteins / metabolism
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Drosophila melanogaster / enzymology
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Drosophila melanogaster / genetics*
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Gene Expression Regulation
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Genes, Reporter
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Green Fluorescent Proteins / genetics
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Green Fluorescent Proteins / metabolism
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Luminescent Proteins / genetics
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Luminescent Proteins / metabolism
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Mitochondria / enzymology
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Mitochondria / genetics*
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Mitochondria / ultrastructure
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Organelle Biogenesis
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Oxidative Phosphorylation
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Protein Stability
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RNA, Double-Stranded / genetics
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RNA, Double-Stranded / metabolism
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Red Fluorescent Protein
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Signal Transduction
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Transcription Factors / genetics*
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Transcription Factors / metabolism
Substances
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DNA, Mitochondrial
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Drosophila Proteins
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Luminescent Proteins
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PN protein, Drosophila
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RNA, Double-Stranded
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TFAM protein, Drosophila
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Transcription Factors
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Green Fluorescent Proteins
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Cyclic AMP
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3',5'-Cyclic-AMP Phosphodiesterases