Metabolic flux analysis in hiPSC-CMs reveals insights into cardiac dysfunction in propionic acidemia DOI Creative Commons
Eva Richard, Hannah Marchuk, Mar Álvarez

et al.

Cellular and Molecular Life Sciences, Journal Year: 2025, Volume and Issue: 82(1)

Published: April 2, 2025

Propionic acidemia is an inborn error of metabolism caused by mutations in either the PCCA or PCCB genes. Patients with propionic experience a range complications, including life-threatening cardiac dysfunctions. However, pathological mechanisms underlying acidemia-associated diseases remain largely unknown. To gain insights into metabolic alterations acidemia, we studied human induced pluripotent stem cell-derived cardiomyocytes generated from patient two pathogenic (p.Cys616_Val633del and p.Gly477Glufs9*) healthy individual. Using stable isotope-based flux analysis, confirmed that lead to impaired propionyl-CoA carboxylase activity cardiomyocytes. In addition being converted propionylcarnitine, accumulated can also be hydrolyzed propionate exported out cell, serving as secondary "pressure valve" regulate cellular levels. Interestingly, deficiency was found shift fuel fatty acid oxidation increased glucose patients acidemia. This switch less energy-efficient may contribute development chronic dysfunction

Language: Английский

Metabolic flux analysis in hiPSC-CMs reveals insights into cardiac dysfunction in propionic acidemia DOI Creative Commons
Eva Richard, Hannah Marchuk, Mar Álvarez

et al.

Cellular and Molecular Life Sciences, Journal Year: 2025, Volume and Issue: 82(1)

Published: April 2, 2025

Propionic acidemia is an inborn error of metabolism caused by mutations in either the PCCA or PCCB genes. Patients with propionic experience a range complications, including life-threatening cardiac dysfunctions. However, pathological mechanisms underlying acidemia-associated diseases remain largely unknown. To gain insights into metabolic alterations acidemia, we studied human induced pluripotent stem cell-derived cardiomyocytes generated from patient two pathogenic (p.Cys616_Val633del and p.Gly477Glufs9*) healthy individual. Using stable isotope-based flux analysis, confirmed that lead to impaired propionyl-CoA carboxylase activity cardiomyocytes. In addition being converted propionylcarnitine, accumulated can also be hydrolyzed propionate exported out cell, serving as secondary "pressure valve" regulate cellular levels. Interestingly, deficiency was found shift fuel fatty acid oxidation increased glucose patients acidemia. This switch less energy-efficient may contribute development chronic dysfunction

Language: Английский

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