ArticleCancer & metabolism2018
Transport-exclusion pharmacology to localize lactate dehydrogenase activity within cells.
Article in Cancer & metabolism, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 17 citations in OpenAlex.
- TLR7/9 and type I interferon signaling reprogram neutrophil NET responses and impair antibacterial defense in systemic lupus erythematosus.Cell press blue · 2026Article
- Protein lactylation in health and diseases: molecular mechanisms, biological significance, and clinical implications.Signal transduction and targeted therapy · 2026Review
- Glycolytic ATP production enables rapid mammalian cell growth.bioRxiv : the preprint server for biology · 2025Article
- A TLR7/9-IFNα-LDHB axis drives vital NET release and compromises antibacterial defense in lupus.bioRxiv : the preprint server for biology · 2025Article
- NFIA regulates articular chondrocyte fatty acid metabolism and joint homeostasis.Science translational medicine · 2025Article
- H3K14 lactylation exacerbates neuronal ferroptosis by inhibiting calcium efflux following intracerebral hemorrhagic stroke.Cell death & disease · 2025Article
- Mitochondria sense bacterial lactate and drive release of neutrophil extracellular traps.Cell host & microbe · 2025Article
- Tumor-derived colorectal cancer organoids induce a unique Treg cell population by directing CD4iScience · 2025Article
- Lactate Utilization Enables Metabolic Escape to Confer Resistance to BET Inhibition in Acute Myeloid Leukemia.Cancer research · 2024Article
- Systems level profiling of chemotherapy-induced stress resolution in cancer cells reveals druggable trade-offs.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Toward spatially resolved metabolomics.Nature chemical biology · 2020Article
- Leveraging insights into cancer metabolism-a symposium report.Annals of the New York Academy of Sciences · 2020Review
- A Metabolism Toolbox for CAR T Therapy.Frontiers in oncology · 2019Review
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
Abstract
backgroundRecent
methodsWithin most mammalian cells, metabolic processes are physically separated by membrane-bound compartments. Our general understanding of this spatial organization and its role in cellular function, however, suffers from the limited number of techniques to localize enzymatic activities within a cell. Here, we describe an approach to assess metabolic compartmentalization by monitoring the activity of pharmacological inhibitors that cannot be transported into specific cellular compartments.
resultsOxamate, which chemically resembles pyruvate, is transported into mitochondria and inhibits LDH activity in purified mitochondria. GSK-2837808A, in contrast, is a competitive inhibitor of NAD, which cannot cross the inner mitochondrial membrane. GSK-2837808A did not inhibit the LDH activity of intact mitochondria, but GSK-2837808A did inhibit LDH activity after the inner mitochondrial membrane was disrupted.
conclusionsOur results are consistent with some mitochondrial LDH that is accessible to oxamate, but inaccessible to GSK-2837808A until mitochondria are homogenized. This strategy of using inhibitors with selective access to subcellular compartments, which we refer to as transport-exclusion pharmacology, is broadly applicable to localize other metabolic reactions within cells.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.