SLC6A6 imports taurine into mitochondria to sustain mitochondrial translation and tumour growth PMID: 41652173

ADC Targets in Oncology

2026-04-10

SLC6A6 imports taurine into mitochondria to sustain mitochondrial translation and tumour growth

Nat Metab. 2026 Mar;8(3):704-721. doi: 10.1038/s42255-026-01455-6.

Liucheng Li ^# ¹ , Jianwei You ^# ¹ , Zi-Qing Chai ^# ² ³ , Xueshan Li ¹ , Xinlei Cai ⁴ ⁵ , Lin Wang ⁴ ⁵ , Fang Yang ¹ , Lingzhi Zhu ¹ , Wen Mi ¹ , Xinyi Xia ¹ , Haohang Yan ¹ , Fei Li ⁴ ⁵ , Juan Wang ¹ , Tong-Jin Zhao ¹ , Ligong Chen ⁶ , Hongbin Ji ⁷ , Pingyu Liu ⁸ , Xiao-Long Zhou ⁹ , Li Chen ¹⁰ , Fuming Li ¹¹

Affiliations

1. Shanghai Key Laboratory of Metabolic Remodeling and Health, Institute of Metabolism and Integrative Biology, Fudan University, Shanghai, China.
2. Key Laboratory of Systems Health Science of Zhejiang Province, School of Life Science, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Hangzhou, China.
3. State Key Laboratory of RNA Innovation, Science and Engineering, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, China.
4. Department of Pathology, School of Basic Medical Sciences, Fudan University, Shanghai, China.
5. Frontier Innovation Center, School of Basic Medical Sciences, Fudan University, Shanghai, China.
6. State Key Laboratory of Membrane Biology, School of Pharmaceutical Sciences, Key Laboratory of Bioorganic Phosphorus Chemistry and Chemical Biology (Ministry of Education), Tsinghua University, Beijing, China.
7. State Key Laboratory of Cell Biology, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, Shanghai, China.
8. Human Phenome Institute, Zhangjiang Fudan International Innovation Center, Fudan University, Shanghai, China.
9. State Key Laboratory of RNA Innovation, Science and Engineering, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, China. [email protected].
10. Shanghai Key Laboratory of Metabolic Remodeling and Health, Institute of Metabolism and Integrative Biology, Fudan University, Shanghai, China. [email protected].
11. Shanghai Key Laboratory of Metabolic Remodeling and Health, Institute of Metabolism and Integrative Biology, Fudan University, Shanghai, China. [email protected].
# Contributed equally.

Abstract

Taurine plays a crucial role in mitochondrial translation. Mammalian cells obtain taurine via exogenous uptake mediated by the plasma membrane transporter SLC6A6 or via cytosolic biosynthesis. However, it remains unclear how taurine enters mitochondria and impacts cellular metabolism. Here we show that SLC6A6, but not exogenous taurine, is essential for Mitochondrial Metabolism and Cancer cell growth. We discover that SLC6A6 also localizes to mitochondria and imports taurine for mitochondrial transfer RNA modifications. SLC6A6 deficiency specifically reduces mitochondrial taurine abundance and abrogates mitochondrial translation and cell proliferation. We identify protein kinase A as a regulator of SLC6A6 subcellular localization, as it promotes SLC6A6 presence at the plasma membrane while inhibiting its mitochondrial localization. Furthermore, we identify NFAT5 as a key regulator of mitochondrial function through SLC6A6 and demonstrate that targeting the NFAT5-SLC6A6 axis markedly impairs mitochondrial translation and tumour growth. Together, these findings suggest that SLC6A6 is a mitochondrial taurine transporter and an exploitable metabolic dependency in Cancer.