Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

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

ABSTRACT: 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.

ORGANISM(S): Homo Sapiens

SUBMITTER: Fuming Li

PROVIDER: PXD071408 | iProX | Sat Nov 29 00:00:00 GMT 2025

REPOSITORIES: iProX

ACCESS DATA

Json Xml

Similar Datasets

Profiling of mRNA localization of nuclear-encoded mitochondrial proteins in zebrafish.

Project description:Current evidence suggests that nuclear-encoded mitochondrial proteins can be locally translated at the mitochondrial surface and co-translationally or post-translationally imported into mitochondria. mRNA localization on the mitochondrial membrane, a prerequisite for localized translation, remains uncharacterized in higher eukaryotic organisms. We employed fractionation-sequencing to profile mitochondria-associated mRNAs in zebrafish larvae. Our transcriptome-wide analysis reveals the localization of mRNAs of only 12% of the nuclear-encoded mitochondrial proteins to the mitochondrial surface, which suggests that post-translational import is the dominant mode of protein import to mitochondria. Additionally, the mRNAs which were localized to the mitochondrial membrane consisted mostly of those encoding proteins involved in mitochondrial dynamics, suggesting their site-specific translation. Finally, we show that the loss of function of the MIA pathway responsible for the post-translational import of a subclass of mitochondrial proteins, triggers mitochondrial localization of mRNAs encoding proteins that are imported to mitochondria via other pathways. Thus, our study suggests that mRNA targeting and localized translation could be relevant in higher eukaryotes to combat stress conditions affecting mitochondrial biogenesis in general.

2023-10-28 | GSE160355 | GEO

MicroRNA Directly Enhances Mitochondrial Translation during Muscle Differentiation.

Project description:MicroRNAs are well known to mediate translational repression and mRNA degradation in the cytoplasm. Various microRNAs have also been detected in membrane-compartmentalized organelles, but the functional significance has remained elusive. Here we report that miR-1, a microRNA specifically induced during myogenesis, efficiently enters the mitochondria where it unexpectedly stimulates, rather than represses, the translation of specific mitochondrial genome-encoded transcripts. We show that this positive effect requires specific miR:mRNA base-pairing and Ago2, but not its functional partner GW182, which is excluded from the mitochondria. We provide evidence for the direct action of Ago2 in mitochondrial translation by Ago2 CrossLinking ImmunoPrecipitation coupled with sequencing (CLIP-seq), functional rescue with mitochondria-targeted Ago2, and selective inhibition of the microRNA machinery in the cytoplasm. These findings unveil a positive function of microRNA in mitochondrial translation and suggest a highly coordinated myogenic program via miR-1 mediated translational stimulation in the mitochondria and repression in the cytoplasm. Examination of miRNA's regulation function in mitochondria in C2C12 myoblasts cells and myotubes cells with CLIP-seq (Ago2).

2014-08-01 | E-GEOD-57596 | biostudies-arrayexpress

Targeting and Plasticity of Mitochondrial Proteins Revealed by Proximity-Specific Ribosome Profiling

Project description:Nearly all mitochondrial proteins are nuclear-encoded and are targeted to their mitochondrial destination from the cytosol. Here, we used proximity-specific ribosome profiling to comprehensively measure translation at the mitochondrial surface in yeast. The majority of inner membrane proteins were co-translationally targeted to mitochondria, reminiscent of proteins entering the endoplasmic reticulum (ER). Comparison between mitochondrial and ER localization demonstrated that the vast majority of proteins were targeted to a specific organelle. A prominent exception was the fumarate reductase Osm1, known to reside in mitochondria. We identified a conserved ER isoform of Osm1, which contributes to the oxidative protein folding capacity of the organelle. This dual localization was enabled by alternative translation initiation sites encoding distinct targeting signals. These findings highlight the exquisite in vivo specificity of organellar targeting mechanisms.

2014-11-10 | GSE61011 | GEO

Delayed protein translocation protects mitochondria against toxic CAT-tailed proteins

Project description:In the ribosome-associated quality control acting on nuclear-encoded mitochondrial proteins (mitoRQC), Vms1 protects mitochondria from toxic effects of Rqc2-generated C-terminal alanyl and threonyl (CAT) tailed proteins that escaped proteosomal degradation facilitated by E3 ubiquitin ligase Ltn1. Here, we performed a genome-wide screen in yeast to identify novel proteins involved in mitoRQC. We found that Pth2, a peptidyl-tRNA hydrolase in the outer mitochondrial membrane, influences aggregation of mitochondrial-targeted CAT-tailed proteins without majorly affecting the CAT-tailing process itself. Peptidyl-tRNA hydrolase activity is essential during this process, however, the activity of Pth2 can be substituted by another peptidyl-tRNA hydrolase, upon proper localization. Our data suggest that Pth2 acts through modulating protein import into mitochondria, enabling CAT-tailed proteins to get access to the cytosolic chaperones and thus relieving the mitochondrial proteostasis network. Other hits obtained in the screen show that, in general, slowing down protein translocation protects mitochondria against toxic CAT-tailed proteins.

2025-11-13 | PXD057575 | Pride

Distinct roles for human mtIF2 and mtIF3 in non-canonical mitochondrial translation.

Project description:The synthesis of mitochondrial OXPHOS complexes is central to cellular metabolism, yet many molecular details of mitochondrial translation remain elusive. It is commonly held view that translation initiation in human mitochondria proceeded in a manner similar to bacterial systems, with the mitoribosomal small subunit bound to the initiation factors, mtIF2 and mtIF3, along with initiator tRNA and an mRNA. However, unlike in bacteria, most human mitochondrial mRNAs lack 5′ leader sequences that can mediate small subunit binding, raising the question of how leaderless mRNAs are recognized by mitoribosomes. By using novel in vitro mitochondrial translation initiation assays, alongside biochemical and genetic characterization of cellular knockouts of mitochondrial translation factors, we describe unique features of translation initiation in human mitochondria. We show that in vitro, leaderless mRNA transcripts can be loaded directly onto assembled 55S mitoribosomes, but not onto the mitoribosomal small subunit (28S). In addition, we demonstrate that while mtIF2 is indispensable for mitochondrial translation, mtIF3 activity is not required for translation of leaderless mitochondrial transcripts but is essential for translation of ATP6 in the case of the bicistronic ATP8/ATP6 transcript. Our results confirm important evolutionary divergences of the mitochondrial translation system, and further our understanding of a process central to eukaryotic metabolism.

2022-12-01 | GSE156937 | GEO

Cell wall integrity is linked to mitochondria and phospholipid homeostasis in Candida albicans through the activity of the post-transcriptional regulator Ccr4-Pop2

Project description:The cell wall is essential for viability of fungi and is an effective drug target in pathogens such as Candida albicans. The contribution of posttranscriptional gene regulators to cell wall integrity in C. albicans is unknown. We show that the C. albicans Ccr4-Pop2 mRNA deadenylase, a regulator of mRNA stability and translation, is required for cell wall integrity. The ccr4/pop2 mutants display reduced wall β-glucans and sensitivity to the echinocandin caspofungin. Moreover, the deadenylase mutants are compromised for filamentation and virulence. We demonstrate that defective cell walls in the ccr4/pop2 mutants are linked to dysfunctional mitochondria and phospholipid imbalance. To further understand mitochondrial function in cell wall integrity, we screened a Saccharomyces cerevisiae collection of mitochondrial mutants. We identify several mitochondrial proteins required for caspofungin tolerance and find a connection between mitochondrial phospholipid homeostasis and caspofungin sensitivity. We focus on the mitochondrial outer membrane SAM complex subunit Sam37, demonstrating it is required for both trafficking of phospholipids between the ER and mitochondria and cell wall integrity. Moreover, in C. albicans also Sam37 is essential for caspofungin tolerance. Our study provides the basis for an integrative view of mitochondrial function in fungal cell wall biogenesis and resistance to echinocandin antifungal drugs. Two-color experimental design comparing cells with a double-knockout of the CCR4 genes to cells with a reintegrated CCR4 gene.

2010-12-10 | E-GEOD-25891 | biostudies-arrayexpress

Metabolic requirements of the metastasis-initiating tumour cell population using oral squamous cell carcinoma (OSCC) as a model system

Project description:Here, we reveal that mitochondrial tRNA methylation is essential for efficient mitochondrial translation to dynamically shape cancer metabolism required for metastasis. Using oral squamous cell carcinoma (OSCC, SCC25 from ATCCR CRL-168TM and patient-derived cell lines with the names VDH01, VDH15) as a model system, we reveal the metabolic requirements of the metastasis-initiating tumour cell population. Only non-dividing tumour cells with high mitochondrial translation rates can invade and disseminate from primary tumours. Thus, inhibition of mitochondrial translation either through deletion of NSUN3 or through pharmacological inhibitors both block metastasis in orthotopic transplantation assays. Together, our study demonstrates that mitochondrial translation controls the metabolic reprogramming required for invasion and dissemination from the primary tumour.

| EGAS00001004765 | EGA

Microarray of heterozygous deletion mutants of yeast ARH1, ATM1, YFH1, and HO (control) genes

Project description:We investigated the transcriptional response of yeast to the loss of a single copy of ARH1; an oxidoreductase of the mitochondrial inner membrane, which is among the few mitochondrial proteins that is essential for viability in yeast, ATM1; the mitochondrial inner membrane ATP-binding cassette (ABC) transporter, and of YFH1; the mitochondrial matrix iron chaperone, which oxidizes and stores iron, and interacts with Isu1p to promote Fe-S cluster assembly.

2019-08-13 | E-MTAB-7648 | biostudies-arrayexpress

C. neoformans gene expression by SIR2 deletion in strains H99 and RC2 subjected to glucose starvation

Project description:Analysis of raw data demonstrated regulation of genes involved in transmembrane transport, transcription and translation; molecular functions that included transporter activity; and cellular components that included the cell membrane, ribosome, nucleolus, and mitochondria

2017-04-25 | GSE74298 | GEO

A genome-scale analysis of mitochondrial-associated mRNAs in plants: upstream AUGs in 5’UTRs alter mRNA targeting

Project description:Intracellular sorting of mRNAs is an essential process to regulate gene expression and protein localization. Most of mitochondrial proteins are nuclear-encoded and imported into mitochondria, through post-translational or co-translational processes. To determine cytosolic mRNAs targeted to the mitochondrial surface, a genome-scale analysis of mRNAs associated with mitochondria has been performed in plants. As expected, many messengers encoding mitochondrial proteins were found associated with mitochondria, but numerous mRNAs encoding cytosolic proteins were also detected. This suggests multiple roles for mRNA targeting, in addition to the co-translational import of mitochondrial proteins. Moreover, correlations between mRNA targeting and function of mitochondrial proteins indicate a coordinated control of mRNAs localization within metabolic pathways. At last, upstream AUGs in 5'UTR, known to regulate translation efficiency of downstream sequences, affect mRNA targeting. A mutational approach coupled with in vivo mRNA visualization confirms this observation, and highlights the role of upstream AUGs as regulators of mRNA targeting to the mitochondrial surface.

2018-08-01 | GSE91388 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data