Reduced methionine synthase expression results in uracil accumulation in mitochondrial DNA and impaired oxidative capacity

Heyden, Katarina; Fiddler, Joanna; Xiu, Yuwen; Malysheva, Olga; Handzlik, Michal K.; Phinney, Whitney N; Stiles, Linsey; Stabler, Sally P.; Metallo, Christian M.; Caudill, Marie A.; Field, Martha S.

doi:10.1093/pnasnexus/pgad105

Cited by 8 publications

(3 citation statements)

References 39 publications

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“…The combination of folate deficiency and SHMT2 deficiency was neither additive nor synergistic in inducing uracil incorporation [5]. This is contrary to Martha's findings in an MTR-deficient model (MTR+/−), where folate deficiency alleviated the uracil incorporation induced by the MTR deficiency [6]. Further studies are needed to resolve the underlying mechanistic differences.…”

Section: Basic Biochemistry Of 1c Metabolismmentioning

confidence: 61%

Notes from the 2022 Folate, Vitamin B12, and One-Carbon Metabolism Conference

2023

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Here, we present notes from the Folate, Vitamin B12, and One-Carbon Metabolism Conference organized by The Federation of American Societies for Experimental Biology (FASEB), held in Asheville, North Carolina, USA, 14–19 August 2022. We aim to share the most recent findings in the field with members of our scientific community who did not attend the meeting and who are interested in the research that was presented. The research described includes discussions of one-carbon metabolism at the biochemical and physiological levels and studies of the role of folate and B12 in development and in the adult, and from bacteria to mammals. Furthermore, the summarized studies address the role of one-carbon metabolism in disease, including COVID-19, neurodegeneration, and cancer.

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Section: Basic Biochemistry Of 1c Metabolismmentioning

confidence: 61%

Notes from the 2022 Folate, Vitamin B12, and One-Carbon Metabolism Conference

2023

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“…Liver genomic DNA was isolated using the High Pure PCR Template Preparation Kit (Roche), followed by RNAse A treatment. As previously described, 2 μg of DNA were treated with uracil DNA glycosylase ( Heyden et al, 2023 ). Samples were derivatized, and uracil levels were quantified using gas chromatography–mass spectrometry ( Fiddler et al, 2021 ).…”

Section: Methodsmentioning

confidence: 99%

Late-life dietary folate restriction reduces biosynthesis without compromising healthspan in mice

Blank,

Hammer,

Boatright

et al. 2024

Life Sci. Alliance

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Folate is a vitamin required for cell growth and is present in fortified foods in the form of folic acid to prevent congenital abnormalities. The impact of low-folate status on life-long health is poorly understood. We found that limiting folate levels with the folate antagonist methotrexate increased the lifespan of yeast and worms. We then restricted folate intake in aged mice and measured various health metrics, metabolites, and gene expression signatures. Limiting folate intake decreased anabolic biosynthetic processes in mice and enhanced metabolic plasticity. Despite reduced serum folate levels in mice with limited folic acid intake, these animals maintained their weight and adiposity late in life, and we did not observe adverse health outcomes. These results argue that the effectiveness of folate dietary interventions may vary depending on an individual’s age and sex. A higher folate intake is advantageous during the early stages of life to support cell divisions needed for proper development. However, a lower folate intake later in life may result in healthier aging.

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“…Liver genomic DNA was isolated using the High Pure PCR Template Preparation Kit (Roche), followed by RNAse A treatment. As previously described, two micrograms of DNA were treated with uracil DNA glycosylase (Heyden et al, 2023). Samples were derivatized, and uracil levels were quantified using gas chromatography-mass spectrometry (Fiddler et al, 2021).…”

Section: Uracil In Genomic Dnamentioning

confidence: 99%

Late-life dietary folate restriction reduces biosynthetic processes without compromising healthspan in mice

Blank,

Hammer,

Boatright

et al. 2024

Preprint

Self Cite

View full text Add to dashboard Cite

Folate is a vitamin required for cell growth and is present in fortified foods in the form of folic acid to prevent congenital abnormalities. The impact of low folate status on life-long health is poorly understood. We found that limiting folate levels with the folate antagonist methotrexate increased the lifespan of yeast and worms. We then restricted folate intake in aged mice and measured various health metrics, metabolites, and gene expression signatures. Limiting folate intake decreased anabolic biosynthetic processes in mice and enhanced metabolic plasticity. Despite reduced serum folate levels in mice with limited folic acid intake, these animals maintained their weight and adiposity late in life, and we did not observe adverse health outcomes. These results argue that the effectiveness of folate dietary interventions may vary depending on an individual’s age and sex. A higher folate intake is advantageous during the early stages of life to support cell divisions needed for proper development. However, a lower folate intake later in life may result in healthier aging.

show abstract

Reduced methionine synthase expression results in uracil accumulation in mitochondrial DNA and impaired oxidative capacity

Cited by 8 publications

References 39 publications

Notes from the 2022 Folate, Vitamin B12, and One-Carbon Metabolism Conference

Notes from the 2022 Folate, Vitamin B12, and One-Carbon Metabolism Conference

Late-life dietary folate restriction reduces biosynthesis without compromising healthspan in mice

Late-life dietary folate restriction reduces biosynthetic processes without compromising healthspan in mice

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