Illuminating NAD+ Metabolism in Live Cells and In Vivo Using a Genetically Encoded Fluorescent Sensor
Illuminating NAD+ Metabolism in Live Cells and In Vivo Using a Genetically Encoded Fluorescent Sensor
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使用基因编码荧光传感器阐明活细胞和体内的 NAD 代谢
DOI：
10.1016/j.devcel.2020.02.017
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发表时间：
2020-04-20
影响因子：
11.8
通讯作者：
Zhao, Yuzheng
中科院分区：
文献类型：
--
作者：
Zou, Yejun;Wang, Aoxue;Zhao, Yuzheng
Understanding of NAD(+) metabolism provides many critical insights into health and diseases, yet highly sensitive and specific detection of NAD(+) metabolism in live cells and in vivo remains difficult. Here, we present ratiometric, highly responsive genetically encoded fluorescent indicators, FiNad, for monitoring NAD(+) dynamics in living cells and animals. FiNad sensors cover physiologically relevant NAD(+) concentrations and sensitively respond to increases and decreases in NAD(+). Utilizing FiNad, we performed a head-to-head comparison study of common NAD(+) precursors in various organisms and mapped their biochemical roles in enhancing NAD(+) levels. Moreover, we showed that increased NAD(+) synthesis controls morphofunctional changes of activated macrophages, and directly imaged NAD+ declines during aging in situ. The broad utility of the FiNad sensors will expand our mechanistic understanding of numerous NAD(+)-associated physiological and pathological processes and facilitate screening for drug or gene candidates that affect uptake, efflux, and metabolism of this important cofactor.
