ArticleCell metabolism2024
Electron transport chain inhibition increases cellular dependence on purine transport and salvage.
Article in Cell metabolism, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers.
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Who cites it
60 citing papers in PubMed.
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- Physiological folate levels constrain nucleotide synthesis and increase dependence on nucleotide salvage.bioRxiv : the preprint server for biology · 2026Article
- Stable Isotope-Resolved Metabolomics in Elucidating Mitochondrial Metabolic Reprogramming and Therapeutic Targets.Biomedical chromatography : BMC · 2026Review
- Copper depletion boosts CNS leukemia therapy by inhibiting nucleotide synthesis through impairment of mitochondrial complex IV activity.Nature cancer · 2026Article
- Dynamic control of nucleotide metabolism in physiology and disease.Nature cell biology · 2026Review
- Loss of heterozygosity exposes germline mutations in complex I and drives Warburg metabolism in oncocytic carcinoma of the thyroid.Science advances · 2026Article
- Reductive death is averted by a conserved de novo lipogenic switch.Molecular cell · 2026Article
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- Pseudomonas aeruginosa Relies on a Phosphoketolase to Support Anaerobic Survival Under Reductive Stress.Molecular microbiology · 2026Article
- Microcephaly-associated protein WDR62 supports purine metabolism by interacting with co-chaperone BAG2.The EMBO journal · 2026Article
- M6A demethylase ALKBH5 mediated Igfbp4 mRNA m6A modification drives fibroblast activation and pathological upper airway fibrosis.Clinical and translational medicine · 2026Article
- The oncogenic control of nucleotide synthesis.Oncogenesis · 2026Review
- UFMylation of Pyruvate Dehydrogenase Regulates Mitochondrial Metabolism.bioRxiv : the preprint server for biology · 2026Article
- A post-translational regulatory map of chronic antigen-driven human T cell dysfunction.bioRxiv : the preprint server for biology · 2026Article
- Aspartate availability drives differential engagement of the malate-aspartate shuttle.Molecular cell · 2026Article
- A shift in the cellular redox state redirects aspartate for export under glucose deprivation.Cancer & metabolism · 2026Article
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Abstract
Mitochondria house many metabolic pathways required for homeostasis and growth. To explore how human cells respond to mitochondrial dysfunction, we performed metabolomics in fibroblasts from patients with various mitochondrial disorders and cancer cells with electron transport chain (ETC) blockade. These analyses revealed extensive perturbations in purine metabolism, and stable isotope tracing demonstrated that ETC defects suppress de novo purine synthesis while enhancing purine salvage. In human lung cancer, tumors with markers of low oxidative mitochondrial metabolism exhibit enhanced expression of the salvage enzyme hypoxanthine phosphoribosyl transferase 1 (HPRT1) and high levels of the HPRT1 product inosine monophosphate. Mechanistically, ETC blockade activates the pentose phosphate pathway, providing phosphoribosyl diphosphate to drive purine salvage supplied by uptake of extracellular bases. Blocking HPRT1 sensitizes cancer cells to ETC inhibition. These findings demonstrate how cells remodel purine metabolism upon ETC blockade and uncover a new metabolic vulnerability in tumors with low respiration.
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