Ultrasensitive sensors reveal the spatiotemporal landscape of lactate metabolism in physiology and disease
Ultrasensitive sensors reveal the spatiotemporal landscape of lactate metabolism in physiology and disease
复制标题
超灵敏传感器揭示生理和疾病中乳酸代谢的时空景观
DOI：
10.1016/j.cmet.2022.10.002
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发表时间：
2023-01-03
期刊：
影响因子：
29
通讯作者：
Zhao, Yuzheng
中科院分区：
文献类型：
--
作者：
Li, Xi;Zhang, Yinan;Zhao, Yuzheng
尽管其在细胞代谢中具有中心重要性，但关于亚细胞乳酸代谢及其在生理学和疾病中的调节的许多细节仍有待确定，因为存在乳酸分布的敏感时空分辨率，并且动力学仍是技术挑战。在这里，我们开发并表征了一种超灵敏，高响应，比率乳酸传感器，名为FiLa，能够监测活细胞和动物中微妙的乳酸波动。利用FiLa，我们证明了乳酸在哺乳动物线粒体中高度富集，并编制了一个亚细胞乳酸代谢图谱，揭示了乳酸作为感知各种代谢活动的关键枢纽。此外，FiLa传感器还能够直接成像糖尿病小鼠中升高的乳酸水平，并有助于建立一种简单、快速和灵敏的乳酸测定方法，用于床旁临床筛查。因此，FiLa传感器提供了强大的，广泛适用的工具，用于定义健康和疾病中乳酸代谢的时空景观。
Despite its central importance in cellular metabolism, many details remain to be determined regarding sub -cellular lactate metabolism and its regulation in physiology and disease, as there is sensitive spatiotemporal resolution of lactate distribution, and dynamics remains a technical challenge. Here, we develop and charac-terize an ultrasensitive, highly responsive, ratiometric lactate sensor, named FiLa, enabling the monitoring of subtle lactate fluctuations in living cells and animals. Utilizing FiLa, we demonstrate that lactate is highly en-riched in mammalian mitochondria and compile an atlas of subcellular lactate metabolism that reveals lactate as a key hub sensing various metabolic activities. In addition, FiLa sensors also enable direct imaging of elevated lactate levels in diabetic mice and facilitate the establishment of a simple, rapid, and sensitive lactate assay for point-of-care clinical screening. Thus, FiLa sensors provide powerful, broadly applicable tools for defining the spatiotemporal landscape of lactate metabolism in health and disease.