{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T21:41:06Z","timestamp":1791495666333,"version":"4.3.4"},"reference-count":42,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2021,1,25]],"date-time":"2021-01-25T00:00:00Z","timestamp":1611532800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Propionic Acidemia Foundation","award":["PAF107"],"award-info":[{"award-number":["PAF107"]}]},{"name":"Spanish Ministry of Economy, Industry and Competitiveness - Agencia Estatal de Investigaci\u00f3n and European Regional Development Fund","award":["SAF2016-76004-R"],"award-info":[{"award-number":["SAF2016-76004-R"]}]},{"DOI":"10.13039\/501100004837","name":"Spanish Ministry of Science and Innovation","doi-asserted-by":"publisher","award":["PID2019-105344RB-I00\/AEI\/10.13039\/501100011033"],"award-info":[{"award-number":["PID2019-105344RB-I00\/AEI\/10.13039\/501100011033"]}],"id":[{"id":"10.13039\/501100004837","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Fundaci\u00f3n Isabel Gemio, Fundaci\u00f3n La Caixa","award":["LCF\/PR\/PR16\/11110018"],"award-info":[{"award-number":["LCF\/PR\/PR16\/11110018"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Propionic acidemia (PA), one of the most frequent life-threatening organic acidemias, is caused by mutations in either the PCCA or PCCB genes encoding both subunits of the mitochondrial propionyl-CoA carboxylase (PCC) enzyme. Cardiac alterations (hypertrophy, dilated cardiomyopathy, long QT) are one of the major causes of mortality in patients surviving the neonatal period. To overcome limitations of current cellular models of PA, we generated induced pluripotent stem cells (iPSCs) from a PA patient with defects in the PCCA gene, and successfully differentiated them into cardiomyocytes. PCCA iPSC-derived cardiomyocytes exhibited reduced oxygen consumption, an accumulation of residual bodies and lipid droplets, and increased ribosomal biogenesis. Furthermore, we found increased protein levels of HERP, GRP78, GRP75, SIG-1R and MFN2, suggesting endoplasmic reticulum stress and calcium perturbations in these cells. We also analyzed a series of heart-enriched miRNAs previously found deregulated in the heart tissue of a PA murine model and confirmed their altered expression. Our novel results show that PA iPSC-cardiomyocytes represent a promising model for investigating the pathological mechanisms underlying PA cardiomyopathies, also serving as an ex vivo platform for therapeutic evaluation.<\/jats:p>","DOI":"10.3390\/ijms22031161","type":"journal-article","created":{"date-parts":[[2021,1,25]],"date-time":"2021-01-25T09:59:40Z","timestamp":1611568780000},"page":"1161","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Cardiomyocytes Derived from Induced Pluripotent Stem Cells as a Disease Model for Propionic Acidemia"],"prefix":"10.3390","volume":"22","author":[{"given":"Esmeralda","family":"Alonso-Barroso","sequence":"first","affiliation":[{"name":"Centro de Biolog\u00eda Molecular Severo Ochoa UAM-CSIC, Universidad Aut\u00f3noma de Madrid, 28049 Madrid, Spain"},{"name":"Centro de Diagn\u00f3stico de Enfermedades Moleculares (CEDEM), 28049 Madrid, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Raras (CIBERER), ISCIII, 28029 Madrid, Spain"},{"name":"Instituto de Investigaci\u00f3n Sanitaria Hospital La Paz (IdiPaz), ISCIII, 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3190-1958","authenticated-orcid":false,"given":"Bel\u00e9n","family":"P\u00e9rez","sequence":"additional","affiliation":[{"name":"Centro de Biolog\u00eda Molecular Severo Ochoa UAM-CSIC, Universidad Aut\u00f3noma de Madrid, 28049 Madrid, Spain"},{"name":"Centro de Diagn\u00f3stico de Enfermedades Moleculares (CEDEM), 28049 Madrid, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Raras (CIBERER), ISCIII, 28029 Madrid, Spain"},{"name":"Instituto de Investigaci\u00f3n Sanitaria Hospital La Paz (IdiPaz), ISCIII, 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2081-0815","authenticated-orcid":false,"given":"Lourdes Ruiz","family":"Desviat","sequence":"additional","affiliation":[{"name":"Centro de Biolog\u00eda Molecular Severo Ochoa UAM-CSIC, Universidad Aut\u00f3noma de Madrid, 28049 Madrid, Spain"},{"name":"Centro de Diagn\u00f3stico de Enfermedades Moleculares (CEDEM), 28049 Madrid, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Raras (CIBERER), ISCIII, 28029 Madrid, Spain"},{"name":"Instituto de Investigaci\u00f3n Sanitaria Hospital La Paz (IdiPaz), ISCIII, 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9711-1417","authenticated-orcid":false,"given":"Eva","family":"Richard","sequence":"additional","affiliation":[{"name":"Centro de Biolog\u00eda Molecular Severo Ochoa UAM-CSIC, Universidad Aut\u00f3noma de Madrid, 28049 Madrid, Spain"},{"name":"Centro de Diagn\u00f3stico de Enfermedades Moleculares (CEDEM), 28049 Madrid, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Raras (CIBERER), ISCIII, 28029 Madrid, Spain"},{"name":"Instituto de Investigaci\u00f3n Sanitaria Hospital La Paz (IdiPaz), ISCIII, 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,1,25]]},"reference":[{"key":"ref_1","unstructured":"Scriver, C.R., Beaudet, A.L., Sly, W., and Valle, D. 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