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

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

doi:10.1016/j.cmet.2022.10.002

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

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

School of Life Sciences

Research output: Contribution to journal › Article › peer-review

83 Scopus citations

Abstract

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.

Original language	English
Pages (from-to)	200-211.e9
Journal	Cell Metabolism
Volume	35
Issue number	1
DOIs	https://doi.org/10.1016/j.cmet.2022.10.002
State	Published - 3 Jan 2023

Keywords

highly responsive lactate sensors
lactate metabolism
point-of-care clinical screening
real-time monitoring
subcellular lactate landscape

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1016/j.cmet.2022.10.002

Cite this

Li, X., Zhang, Y., Xu, L., Wang, A., Zou, Y., Li, T., Huang, L., Chen, W., Liu, S., Jiang, K., Zhang, X., Wang, D., Zhang, L., Zhang, Z., Zhang, Z., Chen, X., Jia, W., Zhao, A., Yan, X., ... Zhao, Y. (2023). Ultrasensitive sensors reveal the spatiotemporal landscape of lactate metabolism in physiology and disease. Cell Metabolism, 35(1), 200-211.e9. https://doi.org/10.1016/j.cmet.2022.10.002

@article{6c0d194d5b034499be0dd6d4b09b230b,

title = "Ultrasensitive sensors reveal the spatiotemporal landscape of lactate metabolism in physiology and disease",

abstract = "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.",

keywords = "highly responsive lactate sensors, lactate metabolism, point-of-care clinical screening, real-time monitoring, subcellular lactate landscape",

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

note = "Publisher Copyright: {\textcopyright} 2022 Elsevier Inc.",

year = "2023",

month = jan,

day = "3",

doi = "10.1016/j.cmet.2022.10.002",

language = "英语",

volume = "35",

pages = "200--211.e9",

journal = "Cell Metabolism",

issn = "1550-4131",

publisher = "Cell Press",

number = "1",

}

Li, X, Zhang, Y, Xu, L, Wang, A, Zou, Y, Li, T, Huang, L, Chen, W, Liu, S, Jiang, K, Zhang, X, Wang, D, Zhang, L, Zhang, Z, Zhang, Z, Chen, X, Jia, W, Zhao, A, Yan, X, Zhou, H, Zhu, L, Ma, X, Ju, Z, Jia, W, Wang, C, Loscalzo, J, Yang, Y & Zhao, Y 2023, 'Ultrasensitive sensors reveal the spatiotemporal landscape of lactate metabolism in physiology and disease', Cell Metabolism, vol. 35, no. 1, pp. 200-211.e9. https://doi.org/10.1016/j.cmet.2022.10.002

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

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 - https://www.scopus.com/pages/publications/85144921286

U2 - 10.1016/j.cmet.2022.10.002

DO - 10.1016/j.cmet.2022.10.002

M3 - 文章

C2 - 36309010

AN - SCOPUS:85144921286

SN - 1550-4131

VL - 35

SP - 200-211.e9

JO - Cell Metabolism

JF - Cell Metabolism

IS - 1

ER -

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

Abstract

Keywords

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this