ArticleeLife2023
Mitochondrial redox adaptations enable alternative aspartate synthesis in SDH-deficient cells.
Article in eLife, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 41 citations in OpenAlex.
- Succinate and lactate produced as conserved biomarkers through chronic and transient substrate-level phosphorylation: from microorganisms to cancer.Journal of bioenergetics and biomembranes · 2026Review
- Adaptive plasticity of aspartate metabolism in succinate dehydrogenase-deficient cancer cells.bioRxiv : the preprint server for biology · 2026Article
- Succinate dehydrogenase loss suppresses pyrimidine biosynthesis via succinate-mediated inhibition of aspartate transcarbamylase.Nature metabolism · 2026Article
- Malic enzyme 2 suppresses PINK1-Parkin-mediated mitophagy by stabilizing ATAD3A via competitive interaction with TRIM25.Cell death & disease · 2026Article
- Receptor-Mitochondria Crosstalk in the Kynurenine Metabolic Pathway: Integrating Metabolomics and Clinical Mass Spectrometry.Antioxidants (Basel, Switzerland) · 2026Review
- Peroxisomal activity drives aggressive bladder cancer phenotypes and reveals erythorbic acid as a potential therapeutic modulator.Frontiers in oncology · 2026Article
- Safety and efficacy of tranexamic acid and beta-blockers for traumatic brain injury: A systematical review and meta-analysis.Surgical neurology international · 2026Article
- Mitochondrial Transplantation Restores Immune Cell Metabolism in Sepsis: A Metabolomics Study.International journal of molecular sciences · 2025Article
- Impact of dietary intervention and supplementation on the physiological profile of individuals with down syndrome.Scientific reports · 2025Article
- Pathway coessentiality mapping reveals complex II is required for de novo purine biosynthesis in acute myeloid leukaemia.Nature metabolism · 2025Article
- p53-mediated regulation of electron transport chain and nucleotide synthesis during Newcastle disease virus infection.Journal of virology · 2025Article
- Rapid generation of a sdhb loss-of-function zebrafish model for secreting pheochromocytomas and paragangliomas.NPJ genomic medicine · 2025Article
- Xenotopic synthetic biology: Prospective tools for delaying aging and age-related diseases.Science advances · 2025Review
- A Mathematical Exploration of SDH-b Loss in Chromaffin Cells.Bulletin of mathematical biology · 2025Article
- Similar deficiencies, different outcomes: succinate dehydrogenase loss in adrenal medulla vs. fibroblast cell culture models of paraganglioma.Cancer & metabolism · 2024Article
- Multi-omics analysis reveals phenylalanine enhance mitochondrial function and hypoxic endurance via LKB1/AMPK activation.Journal of translational medicine · 2024Article
- Succinate Dehydrogenase and Human Disease: Novel Insights into a Well-Known Enzyme.Biomedicines · 2024Review
- Mitochondrial translation is the primary determinant of secondary mitochondrial complex I deficiencies.iScience · 2024Article
- Stable Isotope Tracing Analysis in Cancer Research: Advancements and Challenges in Identifying Dysregulated Cancer Metabolism and Treatment Strategies.Metabolites · 2024Review
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Corrections and comments
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
Abstract
The oxidative tricarboxylic acid (TCA) cycle is a central mitochondrial pathway integrating catabolic conversions of NAD +to NADH and anabolic production of aspartate, a key amino acid for cell proliferation. Several TCA cycle components are implicated in tumorigenesis, including loss-of-function mutations in subunits of succinate dehydrogenase (SDH), also known as complex II of the electron transport chain (ETC), but mechanistic understanding of how proliferating cells tolerate the metabolic defects of SDH loss is still lacking. Here, we identify that SDH supports human cell proliferation through aspartate synthesis but, unlike other ETC impairments, the effects of SDH inhibition are not ameliorated by electron acceptor supplementation. Interestingly, we find aspartate production and cell proliferation are restored to SDH-impaired cells by concomitant inhibition of ETC complex I (CI). We determine that the benefits of CI inhibition in this context depend on decreasing mitochondrial NAD+/NADH, which drives SDH-independent aspartate production through pyruvate carboxylation and reductive carboxylation of glutamine. We also find that genetic loss or restoration of SDH selects for cells with concordant CI activity, establishing distinct modalities of mitochondrial metabolism for maintaining aspartate synthesis. These data therefore identify a metabolically beneficial mechanism for CI loss in proliferating cells and reveal how compartmentalized redox changes can impact cellular fitness.
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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.