文献类型：期刊文献

英文题名：Illuminating NAD+ Metabolism in Live Cells and In Vivo Using a Genetically Encoded Fluorescent Sensor

作者：Zou, Yejun[1,2,3];Wang, Aoxue[1,2,3];Huang, Li[1,3];Zhu, Xudong[4];Hu, Qingxun[1,3];Zhang, Yinan[5];Chen, Xianjun[1,3];Li, Fengwen[5];Wang, Qiaohui[1,3];Wang, Hu[6];Liu, Renmei[1,3];Zuo, Fangting[1,3];Li, Ting[1,3];Yao, Jing[1,3];Qian, Yajin[1,3];Shi, Mei[1,3];Yue, Xiao[1,3];Chen, Weicai[1,3];Zhang, Zhuo[1,3];Wang, Congrong[7];Zhou, Yong[8,9];Zhu, Linyong[1];Ju, Zhenyu[6,10];Loscalzo, Joseph[11];Yang, Yi[1,2];Zhao, Yuzheng[1,3]

机构：[1]East China Univ Sci & Technol, Optogenet & Synthet Biol Interdisciplinary Res Ct, Shanghai Collaborat Innovat Ctr Biomfg Technol,Re, State Key Lab Bioreactor Engn,Chinese Acad Med Sc, 130 Mei Long Rd, Shanghai 200237, Peoples R China;[2]Chinese Acad Sci, Shanghai Inst Biol Sci, CAS Ctr Excellence Brain Sci, Shanghai 200031, Peoples R China;[3]East China Univ Sci & Technol, Shanghai Key Lab New Drug Design, Sch Pharm, 130 Mei Long Rd, Shanghai 200237, Peoples R China;[4]Hangzhou Normal Univ, Inst Ageing Res, Sch Med, 1378 Wenyixi Rd, Hangzhou 311121, Peoples R China;[5]Shanghai Jiao Tong Univ, Affiliated Peoples Hosp 6, Shanghai Key Lab Diabet Mellitus, Metab Dis Biobank, Shanghai 200233, Peoples R China;[6]Jinan Univ, Inst Aging & Regenerat Med, Guangzhou Regenerat Med & Hlth Guangdong Lab, Key Lab Regenerat Med,Minist Educ, Guangzhou 510632, Peoples R China;[7]Tongji Univ, Dept Endocrinol & Metab Dis, Shanghai East Hosp, Translat Med Ctr Stem Cell Therapy,Sch Med, Shanghai 200120, Peoples R China;[8]Wenzhou Med Univ, Sch Ophthalmol & Optometry, 270 Xueyuan Rd, Wenzhou 325027, Zhejiang, Peoples R China;[9]Wenzhou Med Univ, Eye Hosp, 270 Xueyuan Rd, Wenzhou 325027, Zhejiang, Peoples R China;[10]East China Univ Sci & Technol, Sch Chem & Mol Engn, 130 Mei Long Rd, Shanghai 200237, Peoples R China;[11]Harvard Med Sch, Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA

年份：2020

卷号：53

期号：2

起止页码：240

外文期刊名：DEVELOPMENTAL CELL

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000526953300012)】；

基金：We thank Gary Yellen for the PercevalHR vector; Fei Wang, Ping Hu, Yimin Lao, Jing Yi, Chiqi Chen, Junke Zheng, Peili Ni, Yunbin Zhang, Yihong Wang, and Xie Li for technical assistance; and Stephanie C. Tribuna for secretarial assistance. This research is supported by National Key Research and Development Program of China (2017YFA050400 and 2019YFA0904800), NSFC (91649123, 91857202, 31722033, 31671484, 21937004, 91749203, 81525010, and 81420108017), the Shanghai Science and Technology Commission (18JC1411900, 16430723100, 19YF1411400, and 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 Strategic Biobank and Stem Cell Clinical Technology Transformation Platform, ZJ2018-ZD-004), Innovative research team of highlevel local universities in Shanghai, Young Elite Scientists Sponsorship Program by Cast, Shanghai Young Top-notch Talent, the State Key Laboratory of Bioreactor Engineering, the Fundamental Research Funds for the Central Universities, the China Postdoctoral Science Foundation (2019M651413), US National Institutes of Health (HL061795, HG007690, and GM107618), and the American Heart Association (D700382).

语种：英文

摘要：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.