Development and characterization of cell models harbouring mtDNA deletions for i n vitro study of Pearson syndrome
Por:
Hernández-Ainsa C, López-Gallardo E, García-Jiménez MC, Climent-Alcalá FJ, Rodríguez-Vigil C, García Fernández de Villalta M, Artuch-Iriberri R, Montoya J, Ruiz-Pesini E and Emperador S
Publicada:
1 mar 2022
Resumen:
Pearson syndrome is a rare multisystem disease caused by single large-scale mitochondrial DNA deletions (SLSMDs). The syndrome presents early in infancy and is mainly characterised by refractory sideroblastic anaemia. Prognosis is poor and treatment is supportive, thus the development of new models for the study of Pearson syndrome and new therapy strategies is essential. In this work, we report three different cell models carrying an SLMSD: fibroblasts, transmitochondrial cybrids and induced pluripotent stem cells (iPSCs). All studied models exhibited an aberrant mitochondrial ultrastructure and defective oxidative phosphorylation system function, showing a decrease in different parameters, such as mitochondrial ATP, respiratory complex IV activity and quantity or oxygen consumption. Despite this, iPSCs harbouring 'common deletion ' were able to differentiate into three germ layers. Additionally, cybrid clones only showed mitochondrial dysfunction when heteroplasmy level reached 70%. Some differences observed among models may depend on their metabolic profile; therefore, we consider that these three models are useful for the in vitro study of Pearson syndrome, as well as for testing new specific therapies.
Filiaciones:
Hernández-Ainsa C:
Departamento de Bioquímica, Biología Molecular y Celular, Universidad de Zaragoza, 50013 Zaragoza, Spain
Instituto de Investigación Sanitaria de Aragón (IIS-Aragón), 50009 Zaragoza, Spain
Centro de Investigaciones Biomédicas en Red de Enfermedades Raras (CIBERER), 28029 Madrid, Spain
López-Gallardo E:
Departamento de Bioquímica, Biología Molecular y Celular, Universidad de Zaragoza, 50013 Zaragoza, Spain
Instituto de Investigación Sanitaria de Aragón (IIS-Aragón), 50009 Zaragoza, Spain
Centro de Investigaciones Biomédicas en Red de Enfermedades Raras (CIBERER), 28029 Madrid, Spain
García-Jiménez MC:
Servicio de Pediatría. Hospital Universitario Miguel Servet, 50009 Zaragoza, Spain
Climent-Alcalá FJ:
Unidad de Patología Compleja, Servicio de Pediatría. Hospital Universitario La Paz, 28046 Madrid, Spain
Rodríguez-Vigil C:
Servicio de Pediatría. Hospital Universitario Miguel Servet, 50009 Zaragoza, Spain
García Fernández de Villalta M:
Unidad de Patología Compleja, Servicio de Pediatría. Hospital Universitario La Paz, 28046 Madrid, Spain
Artuch-Iriberri R:
Centro de Investigaciones Biomédicas en Red de Enfermedades Raras (CIBERER), 28029 Madrid, Spain
Clinical Biochemistry, Genetics, Pediatric Neurology and Neonatalogy Departments, Institut de Recerca Sant Joan de Déu, 08950 Barcelona, Spain
Montoya J:
Departamento de Bioquímica, Biología Molecular y Celular, Universidad de Zaragoza, 50013 Zaragoza, Spain
Instituto de Investigación Sanitaria de Aragón (IIS-Aragón), 50009 Zaragoza, Spain
Centro de Investigaciones Biomédicas en Red de Enfermedades Raras (CIBERER), 28029 Madrid, Spain
Ruiz-Pesini E:
Departamento de Bioquímica, Biología Molecular y Celular, Universidad de Zaragoza, 50013 Zaragoza, Spain
Instituto de Investigación Sanitaria de Aragón (IIS-Aragón), 50009 Zaragoza, Spain
Centro de Investigaciones Biomédicas en Red de Enfermedades Raras (CIBERER), 28029 Madrid, Spain
Emperador S:
Departamento de Bioquímica, Biología Molecular y Celular, Universidad de Zaragoza, 50013 Zaragoza, Spain
Instituto de Investigación Sanitaria de Aragón (IIS-Aragón), 50009 Zaragoza, Spain
Centro de Investigaciones Biomédicas en Red de Enfermedades Raras (CIBERER), 28029 Madrid, Spain
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