Data Independent Acquisition Mass Spectrometry for Proteomic Advances into Isolated Methylmalonic Acidemia

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.