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

Taurine plays a crucial role in mitochondrial tRNA modification essential for mitochondrial translation. Mammalian cells obtain taurine through plasma membrane transporter SLC6A6-mediated uptake exogenously or 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 tRNA modification. SLC6A6 deficiency specifically reduces mitochondrial taurine abundance and abrogates mitochondrial translation and cell proliferation. Importantly, Protein kinase A dictates SLC6A6 subcellular localization by promoting plasma membrane while inhibiting mitochondrial localization. Furthermore, we show that NFAT5 is a critical regulator of mitochondrial function through SLC6A6, and targeting the NFAT5-SLC6A6 axis significantly limits mitochondrial translation and tumour growth. Together, these findings suggest that SLC6A6 is a mitochondrial taurine transporter and an exploitable metabolic dependency of cancer.