2. Academic Validation
  3. An Ultrasensitive Biosensor for Probing Subcellular Distribution and Mitochondrial Transport of l-2-Hydroxyglutarate

An Ultrasensitive Biosensor for Probing Subcellular Distribution and Mitochondrial Transport of l-2-Hydroxyglutarate

  • Adv Sci (Weinh). 2024 Jul 15:e2404119. doi: 10.1002/advs.202404119.
Zhaoqi Kang 1,  Shuang Hou 1,  Kaiyu Gao 1,  Yidong Liu 1,  Ning Zhang 2,  Zhiqing Fang 3,  Wen Zhang 4,  Xianzhi Xu 1,  Rong Xu 1,  Chuanjuan Lü 1,  Cuiqing Ma 1,  Ping Xu 5,  Chao Gao 1
Affiliations

Affiliations

  • 1 State Key Laboratory of Microbial Technology, Shandong University, Qingdao, 266237, P. R. China.
  • 2 Department of Breast Surgery, General Surgery, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250100, P. R. China.
  • 3 Department of Urology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250100, P. R. China.
  • 4 Institute of Medical Sciences, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250100, P. R. China.
  • 5 State Key Laboratory of Microbial Metabolism, Joint International Research Laboratory of Metabolic & Developmental Sciences, and School of Life Sciences & Biotechnology, Shanghai Jiao Tong University, Shanghai, 200240, P. R. China.
PMID: 39005231 DOI: 10.1002/advs.202404119
Abstract

l-2-Hydroxyglutarate (l-2-HG) is a functionally compartmentalized metabolite involved in various physiological processes. However, its subcellular distribution and mitochondrial transport remain unclear owing to technical limitations. In the present study, an ultrasensitive l-2-HG biosensor, sfLHGFRH, composed of circularly permuted yellow fluorescent protein and l-2-HG-specific transcriptional regulator, is developed. The ability of sfLHGFRH to be used for analyzing l-2-HG metabolism is first determined in human embryonic kidney cells (HEK293FT) and macrophages. Then, the subcellular distribution of l-2-HG in HEK293FT cells and the lower abundance of mitochondrial l-2-HG are identified by the sfLHGFRH-supported spatiotemporal l-2-HG monitoring. Finally, the role of the l-glutamate transporter SLC1A1 in mitochondrial l-2-HG uptake is elucidated using sfLHGFRH. Based on the design of sfLHGFRH, another highly sensitive biosensor with a low limit of detection, sfLHGFRL, is developed for the point-of-care diagnosis of l-2-HG-related diseases. The accumulation of l-2-HG in the urine of patients with kidney Cancer is determined using the sfLHGFRL biosensor.

Keywords

biosensor; l‐2‐hydroxyglutarate; metabolism; mitochondrial transport; point‐of‐care testing.

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