In order to study altered molecular mechanisms representative of the damage induced by the disease in patients, two HEK293 cell models were developed. The first model was obtained with CRISPR/CAS9-based MUT gene knock out (MUT-KO). The second cell model derived from a MUT-KO cell line engineered to rescue the stable expression of MUT protein (MUT-RES). To track the quantitative changes in the global proteome of MUT-KO and MUT-RES cells, a Data Independent Acquisition mass spectrometry-based proteomic experiment was performed.Results and Discussion: Isolated methylmalonic acidemia (MMA) is a rare inherited metabolic disease of propionyl-CoA and branched-chain amino acids catabolism that affects 1 in 100,000 newborn babies. It is caused by a total or partial deficiency of methylmalonyl-CoA mutase enzymatic activity (MUT0 and MUT- subtypes, respectively). Mutations in methylmalonyl-CoA mutase (MUT) gene impair the mitochondrial conversion of methylmalonyl-CoA to succinyl-CoA, metabolized within the Krebs cycle.
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Costanzo, M., Caterino, M., Cevenini, A., Kollipara, L., Shevchuk, O., Nguyen, C. D. L., … Ruoppolo, M. (2020). Data Independent Acquisition Mass Spectrometry for Proteomic Advances into Isolated Methylmalonic Acidemia. In NATO Science for Peace and Security Series A: Chemistry and Biology (pp. 221–223). Springer Science and Business Media B.V. https://doi.org/10.1007/978-94-024-2041-8_15
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