ArticleCell metabolism2025
Machine-learning-guided discovery of SLC25A45 as a mediator of mitochondrial methylated amino acid import and carnitine synthesis.
Article in Cell metabolism, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed.
- SLC25A45 as a prognostic biomarker promotes malignant progression via mutant p53 in hepatocellular carcinoma.Journal of gastrointestinal oncology · 2026Article
- SLC25A35 carrier endows mitochondrial phosphoenolpyruvate with glyceroneogenesis.Life metabolism · 2026Article
- Evolutionary history and recombination in the mitochondrial carrier SLC25 superfamily analyzed by similarities in the exon and transmembrane α-helix sequences.Protein science : a publication of the Protein Society · 2026Article
- Mitochondrial control of amino acid catabolism by a fasting-inducible mitochondrial carrier.Science advances · 2026Article
- Animal models of idiopathic membranous nephropathy: Recent advances and future perspectives.Animal models and experimental medicine · 2026Review
- Specific SLC25 carriers regulate mitochondrial protein synthesis.Science advances · 2026Article
- Mitochondrial control of fuel switching via carnitine biosynthesis.bioRxiv : the preprint server for biology · 2025Article
Corrections and comments
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Authors and funding
11 authors.
Funding
Abstract
Solute carriers (SLCs) regulate cellular and organismal metabolism by transporting small molecules and ions across membranes, yet the physiological substrates of ∼20% remain elusive. To address this, we developed a machine-learning platform to predict gene-metabolite associations. This approach identifies UNC93A and SLC45A4 as candidate plasma membrane transporters for acetylglucosamine and polyamines, respectively. Additionally, we uncover SLC25A45 as a mitochondrial transporter linked to serum levels of methylated basic amino acids, products of protein catabolism. Mechanistically, SLC25A45 is necessary for the mitochondrial import of methylated basic amino acids, including ADMA and TML, the latter serving as a precursor for carnitine synthesis. In line with this observation, SLC25A45 loss impairs carnitine synthesis and blunts upregulation of carnitine-containing metabolites under fasted conditions. By facilitating mitochondrial TML import, SLC25A45 connects protein catabolism to carnitine production, sustaining β-oxidation during fasting. Altogether, our study identifies putative substrates for three SLCs and provides a resource for transporter deorphanization.
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