The cAMP phosphodiesterase Prune localizes to the mitochondrial matrix and promotes mtDNA replication by stabilizing TFAM.

The cAMP phosphodiesterase Prune localizes to the mitochondrial matrix and promotes mtDNA replication by stabilizing TFAM.
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DOI:
10.15252/embr.201439636
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发表时间:
2015-04
期刊:
影响因子:
7.7
通讯作者:
Xu H
Xu H
中科院分区:
生物学2区
文献类型:
--
作者:
Zhang F;Qi Y;Zhou K;Zhang G;Linask K;Xu H

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区室化的 cAMP 信号传导调节线粒体动力学、形态和氧化磷酸化。然而,线粒体 cAMP 通路的调节因子及其对细胞器功能的广泛影响仍有待探索。在这里,我们报告果蝇 Prune 是一种定位于线粒体基质的环核苷酸磷酸二酯酶。敲除培养细胞中的西梅会降低线粒体转录因子 A (TFAM) 和线粒体 DNA (mtDNA) 水平。我们的数据表明 Prune 通过下调线粒体 cAMP 信号传导来稳定 TFAM 并促进线粒体 DNA (mtDNA) 复制。此外,我们的工作证明了线粒体 cAMP 信号在后生动物中的普遍性及其在线粒体生物发生中的新作用。
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.
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