Ultrasensitive sensors reveal the spatiotemporal landscape of lactate metabolism in physiology and disease

Li, Xi; Zhang, Yinan; Xu, Lingya; Wang, Aoxue; Zou, Yejun; Li, Ting; Huang, Li; Chen, Weicai; Liu, Shuning; Jiang, Kun; Zhang, Xiuze; Wang, Dongmei; Zhang, Lijuan; Zhang, Zhuo; Zhang, Zeyi; Chen, Xianjun; Jia, Wei; Zhao, Aihua; Yan, Xinfeng; Zhou, Haimeng; Zhu, Linyong; Ma, Xinran; Ju, Zhenyu; Jia, Weiping; Wang, Congrong^*; Loscalzo, Joseph; Yang, Yi^*; Zhao, Yuzheng^*

Science Citation Index Expanded

华东理工大学; 清华大学; 上海交通大学; 同济大学; 中国医学科学院; 中国科学院; 6; y

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.

关键词

ENCODED FLUORESCENT SENSORS ENERGY-METABOLISM NAD(+) METABOLISM SKELETAL-MUSCLE LIVE CELLS MITOCHONDRIA HOMEOSTASIS DIAGNOSIS DYNAMICS INSULIN