期刊
DEVELOPMENTAL CELL
卷 53, 期 2, 页码 240-+出版社
CELL PRESS
DOI: 10.1016/j.devcel.2020.02.017
关键词
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资金
- National Key Research and Development Program of China [2017YFA050400, 2019YFA0904800]
- NSFC [91649123, 91857202, 31722033, 31671484, 21937004, 91749203, 81525010, 81420108017]
- Shanghai Science and Technology Commission [18JC1411900, 16430723100, 19YF1411400, 19YF1411300]
- Research Unit of New Techniques for Live-cell Metabolic Imaging (Chinese Academy of Medical Sciences) [2019RU01, 2019-I2M-5-013]
- Major Program of Development Fund for Shanghai Zhangjiang National Innovation Demonstration Zone (Stem Cell Clinical Technology Transformation Platform) [ZJ2018-ZD-004]
- Zhangjiang National Innovation Demonstration Zone (Stem Cell Strategic Biobank)
- Innovative research team of highlevel local universities in Shanghai
- Young Elite Scientists Sponsorship Program by Cast
- Shanghai Young Top-notch Talent
- State Key Laboratory of Bioreactor Engineering
- Fundamental Research Funds for the Central Universities
- China Postdoctoral Science Foundation [2019M651413]
- US National Institutes of Health [HL061795, HG007690, GM107618]
- American Heart Association [D700382]
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.
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