ArticleScience translational medicine2022
Aberrant methylmalonylation underlies methylmalonic acidemia and is attenuated by an engineered sirtuin.
Article in Science translational medicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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38 citing papers in PubMed, 49 citations in OpenAlex.
- Targeting MMA-induced USP36 methylmalonylation to suppress macrophage polarization and tumor progression in clear-cell renal cell carcinoma.Cell death and differentiation · 2026Article
- Urinary organic acid levels and their associations with clinical characteristics in patients with schizophrenia.Metabolomics : Official journal of the Metabolomic Society · 2026Article
- Metabolic Perspective on Atherosclerosis: Macrophage Reprogramming and Novel Therapeutic Targets.Journal of the American Heart Association · 2026Review
- [Diagnostic accuracy of tandem mass spectrometry combined with artificial intelligence for neonatal methylmalonic acidemia and associated factors].Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics · 2026Article
- SIRT1 mediates brain metabolic and developmental consequences of methionine synthase deficiency in inborn errors of cobalamin metabolism.Cell reports. Medicine · 2026Article
- Article
- Too Early to Tell? Balancing Diagnostic Accuracy of Newborn Screening for Propionic Acidemia Versus a Timely Referral.International journal of neonatal screening · 2025Article
- Association between methylmalonic acid and prevalence of depression in US adults: evidence from NHANES 2011-2014.European journal of psychotraumatology · 2025Article
- Metabolic toxicity and neurological dysfunction in methylmalonic acidemia: from mechanisms to therapeutics.Molecular medicine (Cambridge, Mass.) · 2025Review
- Animal models of methylmalonic acidemia: insights and challenges.Orphanet journal of rare diseases · 2025Review
- Moxibustion Alleviates Inflammation via SIRT5-mediated Post-translational Modification and Macrophage Polarization.Inflammation · 2025Article
- Metabolic rerouting of valine and isoleucine oxidation increases survival in zebrafish models of disorders of propionyl-CoA metabolism.Human molecular genetics · 2025Article
- Mechanisms of metabolism-coupled protein modifications.Nature chemical biology · 2025Review
- From Nutrient to Nanocarrier: The Multifaceted Role of Vitamin B12 in Drug Delivery.International journal of molecular sciences · 2025Review
- Long-term follow-up of Chinese patients with methylmalonic acidemia of the cblC and mut subtypes.Pediatric research · 2025Article
- SIRT5: a potential target for discovering bioactive natural products.Journal of natural medicines · 2025Review
- Mitochondrial dysfunction drives a neuronal exhaustion phenotype in methylmalonic aciduria.Communications biology · 2025Article
- Methylmalonic acid at the serum level in the elderly contributes to cell growth via mitochondrial dysfunction in colorectal cancer cell spheroids.Biochemistry and biophysics reports · 2025Article
- Case Report: Cerebellar microhemorrhages: an underrecognized feature of MMA-HC revealed by high-field 7.0 T MRI.Frontiers in radiology · 2025Article
- The TRIM33 Bromodomain Recognizes Histone Lysine Lactylation.ACS chemical biology · 2024Article
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12 authors at 2 institutions in 1 country.
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Abstract
Organic acidemias such as methylmalonic acidemia (MMA) are a group of inborn errors of metabolism that typically arise from defects in the catabolism of amino and fatty acids. Accretion of acyl-CoA species is postulated to underlie disease pathophysiology, but the mechanism(s) remain unknown. Here, we surveyed hepatic explants from patients with MMA and unaffected donors, in parallel with samples from various mouse models of methylmalonyl-CoA mutase deficiency. We found a widespread posttranslational modification, methylmalonylation, that inhibited enzymes in the urea cycle and glycine cleavage pathway in MMA. Biochemical studies and mouse genetics established that sirtuin 5 (SIRT5) controlled the metabolism of MMA-related posttranslational modifications. SIRT5 was engineered to resist acylation-driven inhibition via lysine to arginine mutagenesis. The modified SIRT5 was used to create an adeno-associated viral 8 (AAV8) vector and systemically delivered to mutant and control mice. Gene therapy ameliorated hyperammonemia and reduced global methylmalonylation in the MMA mice.
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