TY - JOUR
T1 - Ultrasensitive sensors reveal the spatiotemporal landscape of lactate metabolism in physiology and disease
AU - Li, Xie
AU - Zhang, Yinan
AU - Xu, Lingyan
AU - Wang, Aoxue
AU - Zou, Yejun
AU - Li, Ting
AU - Huang, Li
AU - Chen, Weicai
AU - Liu, Shuning
AU - Jiang, Kun
AU - Zhang, Xiuze
AU - Wang, Dongmei
AU - Zhang, Lijuan
AU - Zhang, Zhuo
AU - Zhang, Zeyi
AU - Chen, Xianjun
AU - Jia, Wei
AU - Zhao, Aihua
AU - Yan, Xinfeng
AU - Zhou, Haimeng
AU - Zhu, Linyong
AU - Ma, Xinran
AU - Ju, Zhenyu
AU - Jia, Weiping
AU - Wang, Congrong
AU - Loscalzo, Joseph
AU - Yang, Yi
AU - Zhao, Yuzheng
N1 - Funding information:
We thank Stephanie C. Tribuna for secretarial assistance. This research is supported 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.).
Publisher Copyright:
© 2022 Elsevier Inc.
PY - 2023/1/3
Y1 - 2023/1/3
N2 - Despite its central importance in cellular metabolism, many details remain to be determined regarding subcellular 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 characterize 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 enriched 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.
AB - Despite its central importance in cellular metabolism, many details remain to be determined regarding subcellular 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 characterize 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 enriched 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.
KW - highly responsive lactate sensors
KW - lactate metabolism
KW - point-of-care clinical screening
KW - real-time monitoring
KW - subcellular lactate landscape
UR - http://www.scopus.com/inward/record.url?scp=85144921286&partnerID=8YFLogxK
U2 - 10.1016/j.cmet.2022.10.002
DO - 10.1016/j.cmet.2022.10.002
M3 - Journal article
C2 - 36309010
AN - SCOPUS:85144921286
SN - 1550-4131
VL - 35
SP - 200-211.e9
JO - Cell Metabolism
JF - Cell Metabolism
IS - 1
ER -
