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Structural basis of augmenting taurine uptake by the taurine transporter in alleviating cellular senescence

Cell Research volume 35, pages 385–388 (2025)Cite this article

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Dear Editor,

Taurine, a sulfur-containing amino acid, plays a crucial role in numerous physiological processes and is essential for the proper functioning of multiple organ systems.1 Taurine deficiency has been implicated in a wide array of health issues, including liver damage, cardiomyopathy, male reproductive impairments, early embryonic developmental disorders, reduced exercise capacity, and accelerated aging.2 The broad spectrum of taurine’s physiological functions underscores its critical importance in metabolic regulation and disease prevention across various tissues. While endogenous taurine is synthesized through the cysteine sulfinic acid pathway, dietary intake serves as the primary source of taurine in the body.2 The absorption and cellular uptake of taurine are primarily facilitated by the taurine transporter (TauT),3 encoded by the SLC6A6 gene. Despite recent studies have highlighted the severe consequences of impaired taurine transport, including tumor progression,4 impaired liver ammonia detoxification,5 and retinal degeneration,6 fundamental questions regarding the substrate binding and transport mechanism of TauT remain unresolved. To address these critical knowledge gaps, our study presents high-resolution cryo-electron microscopy (cryo-EM) structures of TauT in multiple states. By combining these structural insights with functional assays, we provide a comprehensive understanding of the substrate recognition and transport mechanisms of TauT. Furthermore, we demonstrate that enhanced taurine uptake through TauT can alleviate cholangiocyte senescence, as evidenced by our experiments on doxorubicin (Dox)-induced bile duct senescence. This work expands our understanding of TauT’s role in cellular protection and its potential therapeutic applications.

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Fig. 1: Structural insights into TauT and its role in alleviating cellular senescence.

Data availability

The density maps and structure coordinates have been deposited to the Electron Microscopy Data Bank (EMDB) and the Protein Data Bank (PDB). TauT-DDM apo: accession numbers EMD-61451 and PDB-9JG5; TauT-Saposin A apo: accession numbers EMD-61450 and PDB-9JG4; TauT-Saposin A-taurine inward: accession numbers EMD-62147 and PDB-9K7B; TauT-Saposin A-taurine occluded: accession numbers EMD-62150 and PDB-9K7N.

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Acknowledgements

The cryo-EM data were collected at the Advanced Center for Electron Microscopy, Shanghai Institute of Materials Medicine (SIMM). We sincerely thank the collaborative efforts of all staff, particularly Dr. Xuemei Yang, Dr. Canrong Wu, Miss Wen Hu, Miss Shuai Li and Mr Kai Wu for their invaluable assistance in cryo-EM data collection and structure determination. We express our appreciation to Dr. Junrui Li for providing data processing. We express our appreciation for providing experimental instruments from the Experimental Nuclear Medicine Laboratory, Core Facility of Basic Medical Sciences, Shanghai Jiao Tong University School of Medicine. We express our appreciation to Dr. Huahua Song for providing experimental instruments. This work was partially supported by the National Key R&D Program of China (2022YFC2703105 to H.E.X.), the National Natural Science Foundation of China (82330018 to X.M.), and the CAS Strategic Priority Research Program (XDB37030103 to H.E.X.).

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Author notes

  1. These authors contributed equally: Heng Zhang, Nana Cui.

Authors and Affiliations

  1. The State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China

    Heng Zhang & H. Eric Xu

  2. Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, State Key Laboratory for Oncogenes and Related Genes, NHC Key Laboratory of Digestive Diseases, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Institute of Digestive Disease, Shanghai, China

    Nana Cui & Xiong Ma

  3. Institute of Aging & Tissue Regeneration, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China

    Xiong Ma

  4. The Shanghai Advanced Electron Microscope Center, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China

    H. Eric Xu

Authors
  1. Heng Zhang
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  2. Nana Cui
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  3. Xiong Ma
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  4. H. Eric Xu
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Contributions

H.Z. initiated and conceived this project in collaboration with N.N.C. H.Z. designed the expression constructs, purified the TauT protein samples, prepared cryo-EM grids, calculated cryo-EM data, built and refined structural models, prepared figures and wrote the manuscript. N.N.C. conducted the transport assay, cell proliferation, RT-PCR, western blot, and RNA-Seq, performed aging-related assays, and prepared figures. H.E.X., in collaboration with X.M., supervised the project. H.E.X. edited the manuscript.

Corresponding authors

Correspondence to Xiong Ma or H. Eric Xu.

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The authors declare no competing interests.

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Supplementary information

41422_2025_1090_MOESM1_ESM.pdf

Supplementary information_Structural basis of augment taurine uptake by taurine transporter alleviating cellular senescence

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Zhang, H., Cui, N., Ma, X. et al. Structural basis of augmenting taurine uptake by the taurine transporter in alleviating cellular senescence. Cell Res 35, 385–388 (2025). https://doi.org/10.1038/s41422-025-01090-y

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