In a groundbreaking study published in Nature Metabolism, researchers have unveiled a critical link between taurine uptake and mitochondrial function that could redefine our understanding of cancer metabolism. The study identifies the protein SLC6A6 not only as a plasma membrane transporter responsible for taurine uptake in mammalian cells but also as a pivotal transporter of taurine into mitochondria. This mitochondrial role of SLC6A6 fundamentally supports mitochondrial translation and, by extension, tumor cell proliferation, revealing a novel metabolic vulnerability that could be exploited in cancer therapy.
Taurine, a sulfur-containing β-amino acid, has long been recognized for its abundance in mammalian tissues and its roles in osmoregulation, antioxidation, and bile salt formation. However, the mechanisms by which taurine influences mitochondrial activity remained obscure until now. While taurine’s cytosolic biosynthesis and uptake through the plasma membrane transporter SLC6A6 were characterized, the pathway for its entry into mitochondria and subsequent impact on mitochondrial protein synthesis was previously undefined.
The research team utilized advanced cellular and molecular techniques to demonstrate that SLC6A6 localizes not only to the plasma membrane but intriguingly also to mitochondria. This dual localization allows SLC6A6 to import taurine directly into mitochondria, a process essential for proper mitochondrial function. Specifically, taurine imported via mitochondrial SLC6A6 is required for the modification of mitochondrial transfer RNAs, a post-transcriptional process critical for accurate and efficient mitochondrial translation.
Loss-of-function experiments provided compelling evidence of SLC6A6’s indispensability for mitochondrial metabolism and cell growth. Cells deficient in SLC6A6 exhibited dramatic reductions in mitochondrial taurine content, which led to impaired mitochondrial translation. This defect cascaded into decreased cellular proliferation, highlighting the integral role of SLC6A6 in maintaining mitochondrial activity and supporting the bioenergetic and anabolic demands of rapidly dividing cancer cells.
One of the more striking findings of this work was the differential impact of exogenous taurine supplementation versus SLC6A6 expression. While cells can uptake taurine from the extracellular environment, simply supplying exogenous taurine was insufficient to rescue mitochondrial dysfunction caused by SLC6A6 loss. This underscores that the presence and localization of SLC6A6, rather than extracellular taurine concentration alone, are critical determinants of mitochondrial taurine availability and function.
The study also delved into regulatory mechanisms controlling SLC6A6 subcellular distribution. Protein kinase A (PKA), a well-known signaling enzyme, was shown to direct the localization of SLC6A6. PKA activity favors the plasma membrane presence of SLC6A6 while concomitantly inhibiting its mitochondrial localization. This dynamic shuttling suggests that cells may finely tune taurine transport into mitochondria via signaling pathways, adapting mitochondrial function to physiological and environmental cues.
Further investigation identified the transcription factor NFAT5 as a key regulator within this metabolic axis. NFAT5 influences mitochondrial function indirectly by controlling SLC6A6 expression. Perturbation of the NFAT5–SLC6A6 pathway was found to profoundly disrupt mitochondrial translation and reduce tumor growth in preclinical models. These findings position NFAT5 as a central node integrating cellular stress signals and metabolic requirements through taurine transport.
This work challenges established paradigms by revealing that mitochondrial translation is not solely regulated by canonical nuclear-encoded factors but also relies on specific metabolite transporters present within the organelle. The direct import of taurine via SLC6A6 provides an essential substrate for mitochondrial tRNA modifications, which are fundamental to the fidelity and efficiency of mitochondrial protein synthesis.
Given the heightened metabolic demands of cancer cells and their reliance on mitochondrial function for energy production and biosynthesis, targeting components of the NFAT5–SLC6A6 axis presents an attractive therapeutic strategy. Inhibiting taurine import into mitochondria can selectively disrupt tumor cell proliferation without necessarily impacting normal cells, offering a potential avenue for precision oncology.
Moreover, the discovery of mitochondrial SLC6A6 adds a new layer of complexity to mitochondrial metabolite transport. Unlike previously characterized transporters, SLC6A6’s dual localization and functional versatility in both plasma membrane taurine uptake and mitochondrial import highlight a sophisticated metabolic adaptation mechanism cancer cells employ for growth and survival.
The study also opens questions about the broader role of taurine in mitochondrial biology beyond cancer. Since mitochondrial translation is universally vital for cellular respiration and homeostasis, it is possible that SLC6A6-mediated taurine transport plays critical roles in other proliferative or stress-responsive contexts.
This research utilized a suite of cutting-edge methods, including subcellular fractionation, mitochondrial isolation, taurine quantification via mass spectrometry, and mitochondrial translation assays. The rigorous approach enabled precise determination of taurine distribution dynamics and functional consequences of SLC6A6 manipulation in multiple cancer cell lines.
Furthermore, the identification of protein kinase A as a regulator of SLC6A6 localization underscores the intersection of signal transduction and metabolic control. This may have profound implications for understanding how extracellular signals are translated into metabolic reprogramming, a hallmark of cancer evolution and therapeutic resistance.
In light of these findings, future therapeutic designs could involve combinatorial approaches that harness metabolic inhibitors targeting the NFAT5–SLC6A6 axis alongside established chemotherapies. Additionally, these insights may inspire the development of diagnostic biomarkers based on SLC6A6 expression or mitochondrial taurine levels to stratify patients likely to benefit from such treatments.
In conclusion, the elucidation of SLC6A6 as a mitochondrial taurine transporter establishes a previously unrecognized metabolic dependency in cancer cells. By linking taurine import to mitochondrial translation and tumor growth, this study not only deepens our understanding of mitochondrial biology but also highlights novel targets for anticancer intervention. The implications of this discovery resonate beyond oncology, potentially informing research on mitochondrial diseases and metabolic disorders where impaired mitochondrial translation contributes to pathology.
This paradigm-shifting work thus propels taurine and its transporter SLC6A6 into the spotlight as key players in mitochondrial function and cancer metabolism, promising new directions for research and therapeutic innovation.
Subject of Research:
Mitochondrial translation regulation and tumor metabolism via taurine transport
Article Title:
SLC6A6 imports taurine into mitochondria to sustain mitochondrial translation and tumour growth
Article References:
Li, L., You, J., Chai, ZQ. et al. SLC6A6 imports taurine into mitochondria to sustain mitochondrial translation and tumour growth. Nat Metab (2026). https://doi.org/10.1038/s42255-026-01455-6
Image Credits:
AI Generated
DOI:
https://doi.org/10.1038/s42255-026-01455-6
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