Mitochondrial Ca2+ mobilization is a key element in olfactory signaling
Mitochondrial Ca2+ mobilization is a key element in olfactory signaling
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DOI：
10.1038/nn.3074
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发表时间：
2012-05-01
影响因子：
25
通讯作者：
Spehr, Marc
中科院分区：
文献类型：
--
作者：
Fluegge, Daniela;Moeller, Lisa M.;Spehr, Marc
在嗅觉感觉神经元（OSNs）中，胞质Ca2+控制嗅觉信号的增益和敏感性。已经描述了协调OSN Ca2+动力学的分子机制的重要组成部分，但关键细节仍然缺失。在这里，我们证明了线粒体Ca2+动员在小鼠osn中的关键生理作用。结合新的线粒体！通过膜片钳记录、细胞器迁移率测定和超微结构分析，我们的研究确定线粒体是嗅觉信号的关键决定因素。我们发现，在感觉刺激期间，线粒体Ca2+动员塑造了OSNs细胞质Ca2+反应谱，确保了广泛的动态响应范围，并保持了spike产生机制的敏感性。当线粒体功能受损时，嗅觉神经元的功能是简单的刺激探测器，而不是强度编码器。此外，我们还描述了线粒体向嗅觉旋钮的活动依赖性募集，这一机制为osn提供了一种环境依赖性工具，以维持细胞稳态和信号完整性。
In olfactory sensory neurons (OSNs), cytosolic Ca2+ controls the gain and sensitivity of olfactory signaling. Important components of the molecular machinery that orchestrates OSN Ca2+ dynamics have been described, but key details are still missing. Here, we demonstrate a critical physiological role of mitochondrial Ca2+ mobilization in mouse OSNs. Combining a new mitochondria! Ca2+ imaging approach with patch-clamp recordings, organelle mobility assays and ultrastructural analyses, our study identifies mitochondria as key determinants of olfactory signaling. We show that mitochondrial Ca2+ mobilization during sensory stimulation shapes the cytosolic Ca2+ response profile in OSNs, ensures a broad dynamic response range and maintains sensitivity of the spike generation machinery. When mitochondrial function is impaired, olfactory neurons function as simple stimulus detectors rather than as intensity encoders. Moreover, we describe activity-dependent recruitment of mitochondria to olfactory knobs, a mechanism that provides a context-dependent tool for OSNs to maintain cellular homeostasis and signaling integrity.