Functional TASK-3-Like Channels in Mitochondria of Aldosterone-Producing Zona Glomerulosa Cells.
Functional TASK-3-Like Channels in Mitochondria of Aldosterone-Producing Zona Glomerulosa Cells.
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DOI：
10.1161/hypertensionaha.116.08871
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发表时间：
2017-08
期刊：
影响因子：
--
通讯作者：
Barrett PQ
中科院分区：
文献类型：
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作者：
Yao J;McHedlishvili D;McIntire WE;Guagliardo NA;Erisir A;Coburn CA;Santarelli VP;Bayliss DA;Barrett PQ
Ca2+ 驱动肾上腺球状带 (ZG) 细胞的胞浆和线粒体区室中醛固酮的合成。每个区室的膜电位调节 Ca2+ 信号的幅度；然而，只有质膜离子通道及其在调节细胞膜电位中的作用作为人类醛固酮增多症的病理原因引起了研究关注。此前，我们报道了在 ZG 细胞的细胞膜电位没有变化的情况下，小鼠 TASK-3 通道的基因缺失会产生醛固酮过量。在这里，我们使用酵母双杂交、免疫沉淀和电子显微镜分析发现 TASK-3 通道驻留在线粒体中，调节线粒体形态、线粒体膜电位 (mitoVm) 和醛固酮的产生。这项研究提供了原理证明，即线粒体 K+ 通道通过调节线粒体内膜形态和 mitoVm，能够在类固醇生成细胞的醛固酮失调中发挥病理作用。
Ca2+ drives aldosterone synthesis in the cytosolic and mitochondrial compartments of the adrenal zona glomerulosa (ZG) cell. Membrane potential across each of these compartments regulates the amplitude of the Ca2+ signal; yet, only plasma membrane ion channels and their role in regulating cell membrane potential have garnered investigative attention as pathological causes of human hyperaldosteronism. Previously, we reported that genetic deletion of TASK-3 channels from mice produces aldosterone excess in the absence of a change in the cell membrane potential of ZG cells. Here, we report using yeast two-hybrid, immunoprecipitation and electron microscopic analyses that TASK-3 channels are resident in mitochondria, where they regulate mitochondrial morphology, mitochondrial membrane potential (mitoVm) and aldosterone production. This study provides proof-of-principle that mitochondrial K+ channels, by modulating inner mitochondrial membrane morphology and mitoVm, have the ability to play a pathological role in aldosterone dysregulation in steroidogenic cells.