ArticleRedox biology2014
Sources of superoxide/H2O2 during mitochondrial proline oxidation.
Article in Redox biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 77 citations in OpenAlex.
- Circulating metabolites associated with protection against Mycobacterium tuberculosis infection and inhibition of mycobacterial growth.Communications biology · 2026Article
- Proline Metabolism in Cancer: Emerging Roles in Redox Homeostasis and Therapeutic Opportunities.Cancers · 2025Review
- Proline dehydrogenase, a rate-limiting catabolic enzyme, affecting the growth and pathogenicity of Toxoplasma gondii tachyzoites by regulating the proline metabolism and mitochondrial function of the parasite.Parasites & vectors · 2025Article
- Stage-resolved transcriptomic profiling ofFrontiers in insect science · 2025Article
- Loss of mitochondrial pyruvate carrier 1 supports proline-dependent proliferation and collagen biosynthesis in ovarian cancer.Molecular metabolism · 2024Article
- Proline catabolism is a key factor facilitating Candida albicans pathogenicity.PLoS pathogens · 2023Article
- Mitochondrial proteins encoded by the 22q11.2 neurodevelopmental locus regulate neural stem and progenitor cell proliferation.Molecular psychiatry · 2023Article
- The Role of Proton-Coupled Amino Acid Transporter 2 (SLC36A2) in Cold-Induced Thermogenesis of Mice.Nutrients · 2023Article
- Appraising the Role of Astrocytes as Suppliers of Neuronal Glutathione Precursors.International journal of molecular sciences · 2023Review
- Site IQ in mitochondrial complex I generates S1QEL-sensitive superoxide/hydrogen peroxide in both the reverse and forward reactions.The Biochemical journal · 2023Article
- Mitochondrial genes in the 22q11.2 deleted region regulate neural stem and progenitor cell proliferation.bioRxiv : the preprint server for biology · 2023Article
- Can proline dehydrogenase-a key enzyme involved in proline metabolism-be a novel target for cancer therapy?Frontiers in oncology · 2023Review
- Conditions Conducive to the Glutathionylation of Complex I Subunit NDUFS1 Augment ROS Production following the Oxidation of Ubiquinone Linked Substrates, Glycerol-3-Phosphate and Proline.Antioxidants (Basel, Switzerland) · 2022Article
- Mitochondrial ROS signalling requires uninterrupted electron flow and is lost during ageing in flies.GeroScience · 2022Article
- Effects of sugars, fatty acids and amino acids on cytosolic and mitochondrial hydrogen peroxide release from liver cells.Free radical biology & medicine · 2022Article
- Interplay between Proline Metabolism and ROS in the Fine Tuning of Root-Meristem Size inPlants (Basel, Switzerland) · 2022Article
- Intriguing Role of Proline in Redox Potential Conferring High Temperature Stress Tolerance.Frontiers in plant science · 2022Review
- Crosstalk between Neuron and Glial Cells in Oxidative Injury and Neuroprotection.International journal of molecular sciences · 2021Review
- N-Propargylglycine: a unique suicide inhibitor of proline dehydrogenase with anticancer activity and brain-enhancing mitohormesis properties.Amino acids · 2021Article
- Glutamine Homeostasis and Its Role in the Adaptive Strategies of the Blind Mole Rat, Spalax.Metabolites · 2021Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
p53 Inducible gene 6 (PIG6) encodes mitochondrial proline dehydrogenase (PRODH) and is up-regulated several fold upon p53 activation. Proline dehydrogenase is proposed to generate radicals that contribute to cancer cell apoptosis. However, there are at least 10 mitochondrial sites that can produce superoxide and/or H2O2, and it is unclear whether proline dehydrogenase generates these species directly, or instead drives production by other sites. Amongst six cancer cell lines, ZR75-30 human breast cancer cells had the highest basal proline dehydrogenase levels, and mitochondria isolated from ZR75-30 cells consumed oxygen and produced H2O2 with proline as sole substrate. Insects use proline oxidation to fuel flight, and mitochondria isolated from Drosophila melanogaster were even more active with proline as sole substrate than ZR75-30 mitochondria. Using mitochondria from these two models we identified the sites involved in formation of superoxide/H2O2 during proline oxidation. In mitochondria from Drosophila the main sites were respiratory complexes I and II. In mitochondria from ZR75-30 breast cancer cells the main sites were complex I and the oxoglutarate dehydrogenase complex. Even with combinations of substrates and respiratory chain inhibitors designed to minimize the contributions of other sites and maximize any superoxide/H2O2 production from proline dehydrogenase itself, there was no significant direct contribution of proline dehydrogenase to the observed H2O2 production. Thus proline oxidation by proline dehydrogenase drives superoxide/H2O2 production, but it does so mainly or exclusively by providing anaplerotic carbon for other mitochondrial dehydrogenases and not by producing superoxide/H2O2 directly.
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