ReviewThe Biochemical journal2021
Consequences of NaCT/SLC13A5/mINDY deficiency: good versus evil, separated only by the blood-brain barrier.
Review in The Biochemical journal, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 35 citations in OpenAlex.
- The role of γ-aminobutyric acid and its receptor in metabolic reprogramming and tumor progression.Biochemistry and biophysics reports · 2026Review
- Potential Biological Processes Related to Brain SLC13A5 Across the Lifespan: Weighted Gene Co-Expression Network Analysis from Large Human Transcriptomic Data.Brain sciences · 2026Article
- Accelerated osteocytic citrate production in chronic kidney disease is associated with protection of the kidney.bioRxiv : the preprint server for biology · 2025Article
- Elucidation of the structure and molecular mechanisms of the aspartate antiporter.Communications biology · 2025Article
- Regulatory interaction between metabolite transporters coordinates glucose and exometabolite fluxes to drive bioenergetics.Nature communications · 2025Article
- Citrate Transporter Expression and Localization: TheInternational journal of molecular sciences · 2025Article
- A genetic driver of epileptic encephalopathy impairs gating of synaptic glycolysis.bioRxiv : the preprint server for biology · 2025Article
- Potassium/Sodium Citrate Attenuates Paclitaxel-Induced Peripheral Neuropathy.International journal of molecular sciences · 2025Article
- Membrane transporter progressive ankylosis protein homologue (Frontiers in aging · 2025Article
- Molecular Phenotypes Segregate Missense Mutations in SLC13A5 Epilepsy.Journal of molecular biology · 2024Article
- Article
- Novel Approaches to Studying SLC13A5 Disease.Metabolites · 2024Review
- The citrate transporter SLC13A5 as a therapeutic target for kidney disease: evidence from Mendelian randomization to inform drug development.BMC medicine · 2023Article
- Targeting Longevity GeneMetabolites · 2023Article
- Sis2 regulates yeast replicative lifespan in a dose-dependent manner.Nature communications · 2023Article
- Mapping the Metabolic Niche of Citrate Metabolism andMetabolites · 2023Review
- A specialized metabolic pathway partitions citrate in hydroxyapatite to impact mineralization of bones and teeth.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Review
- A Novel and Cross-Species Active Mammalian INDY (NaCT) Inhibitor Ameliorates Hepatic Steatosis in Mice with Diet-Induced Obesity.Metabolites · 2022Article
- Untargeted Metabolomics of Slc13a5 Deficiency Reveal Critical Liver-Brain Axis for Lipid Homeostasis.Metabolites · 2022Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
NaCT/SLC13A5 is a Na+-coupled transporter for citrate in hepatocytes, neurons, and testes. It is also called mINDY (mammalian ortholog of 'I'm Not Dead Yet' in Drosophila). Deletion of Slc13a5 in mice leads to an advantageous phenotype, protecting against diet-induced obesity, and diabetes. In contrast, loss-of-function mutations in SLC13A5 in humans cause a severe disease, EIEE25/DEE25 (early infantile epileptic encephalopathy-25/developmental epileptic encephalopathy-25). The difference between mice and humans in the consequences of the transporter deficiency is intriguing but probably explainable by the species-specific differences in the functional features of the transporter. Mouse Slc13a5 is a low-capacity transporter, whereas human SLC13A5 is a high-capacity transporter, thus leading to quantitative differences in citrate entry into cells via the transporter. These findings raise doubts as to the utility of mouse models to evaluate NaCT biology in humans. NaCT-mediated citrate entry in the liver impacts fatty acid and cholesterol synthesis, fatty acid oxidation, glycolysis, and gluconeogenesis; in neurons, this process is essential for the synthesis of the neurotransmitters glutamate, GABA, and acetylcholine. Thus, SLC13A5 deficiency protects against obesity and diabetes based on what the transporter does in hepatocytes, but leads to severe brain deficits based on what the transporter does in neurons. These beneficial versus detrimental effects of SLC13A5 deficiency are separable only by the blood-brain barrier. Can we harness the beneficial effects of SLC13A5 deficiency without the detrimental effects? In theory, this should be feasible with selective inhibitors of NaCT, which work only in the liver and do not get across the blood-brain barrier.
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