文献类型：期刊文献

英文题名：Ultrasensitive sensors reveal the spatiotemporal landscape of lactate metabolism in physiology and disease

作者：Li, Xi[1,2,3];Zhang, Yinan[4];Xu, Lingya[5,6];Wang, Aoxue[1,2,3];Zou, Yejun[1,2,3];Li, Ting[1,2,3];Huang, Li[1];Chen, Weicai[1];Liu, Shuning[1];Jiang, Kun[1];Zhang, Xiuze[1];Wang, Dongmei[5,6];Zhang, Lijuan[1];Zhang, Zhuo[1,2,3];Zhang, Zeyi[1];Chen, Xianjun[1,2,3];Jia, Wei[4];Zhao, Aihua;Yan, Xinfeng[7];Zhou, Haimeng[8];Zhu, Linyong[1];Ma, Xinran[5,6];Ju, Zhenyu[9];Jia, Weiping[4];Wang, Congrong[10];Loscalzo, Joseph;Yang, Yi[1,3];Zhao, Yuzheng[1,2]

机构：[1]East China Univ Sci & Technol, Optogenet & Synthet Biol Interdisciplinary Res Ctr, Shanghai Frontiers Sci Ctr Optogenet Tech Cell Met, State Key Lab Bioreactor Engn,Sch Pharm, 130 Mei Long Rd, Shanghai 200237, Peoples R China;[2]Chinese Acad Med Sci, Res Unit New Tech Live Cell Metab Imaging, Beijing 100730, Peoples R China;[3]Chinese Acad Sci, Shanghai Inst Biol Sci, CAS Ctr Excellence Brain Sci, Shanghai 200031, Peoples R China;[4]Shanghai Jiao Tong Univ Affiliated Peoples Hosp 6, Ctr Translat Med, Metab Dis Biobank, 600 Yishan Rd, Shanghai 200233, Peoples R China;[5]East China Normal Univ, Inst Biomed Sci, Shanghai Key Lab Regulatory Biol, 500 Dongchuan Rd, Shanghai 200241, Peoples R China;[6]East China Normal Univ, Sch Life Sci, 500 Dongchuan Rd, Shanghai 200241, Peoples R China;[7]Tongji Univ, Shanghai East Hosp, Translat Med Ctr Stem Cell Therapy, Dept Endocrinol,Sch Med, Shanghai 200120, Peoples R China;[8]Tsinghua Univ, Zhejiang Prov Key Lab Appl Enzymol, Yangtze Delta Reg Inst, Jiaxing 314006, Peoples R China;[9]Jinan Univ, Inst Aging & Regenerat Med, Guangzhou Regenerat Med & Hlth Guangdong Lab, Key Lab Regenerat Med,Minist Educ, Guangzhou 510632, Peoples R China;[10]Harvard Med Sch, Brigham & Womens Hosp, Dept Med, Sch Med, Boston, MA 02115 USA

年份：2023

卷号：35

期号：1

起止页码：200

外文期刊名：CELL METABOLISM

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000920390700001)】；

基金：We thank Stephanie C. Tribuna for secretarial assistance. This research is sup- ported by National Key Research and Development Program of China (2019YFA0904800 to Y. Zhao and 2021YFA0804900 to A.W.) , NSFC (32121005, 32150030, 32030065, and 92049304 to Y.Zhao; 91857202, 21937004, and 32150028 to Y.Y.; 91749203 and 82030039 to Z.J.; 82070913 to C.W.; 81770883 to Y. Zhang; 31900833 to X.L.; 32000920 to A.W.; 31901033 to T.L.; and 32201230 to Y. Zou) , the Shanghai Science and Technology Commission (19YF1411400 to A.W. and 19YF1411300 to T.L.) , the Shanghai Frontiers Science Center of Optogenetic Techniques for Cell Metabolism (Y. Zhao) , the Research Unit of New Techniques for Live-cell Metabolic Imaging (Chinese Academy of Medical Sciences, 2019-I2M-5-013 to Y. Zhao) , the innovative research team of high-level local universities in Shanghai, the State Key Laboratory of Bioreactor Engineering, the Fundamental Research Funds for the Central Universities, US National Institutes of Health (HL119145, HL155107, HL155096, and HG007690 to J.L.) , and the American Heart Association (D700382 and AHA2020CV-19 to J.L.) .

语种：英文

摘要：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.