Development and characterization of different cell models harbouring mitochondrial DNA deletions for in vitro study of Pearson syndrome

Pearson syndrome (PS) is a rare multisystem disease caused by single large scale mitochondrial DNA deletions (SLSMDs). PS presents early in infancy and it is mainly characterized by refractory sideroblastic anaemia. Prognosis is poor and treatment is supportive, thus development of new models for the study of PS and new therapy strategies is essential. In this work we report three different cell models carrying a SLMSD: fibroblasts, transmitochondrial cybrids and induced pluripotent stem cells (iPSC). All studied models exhibited an aberrant mitochondrial ultrastructure and defective OXPHOS function, showing a decrease in different parameters such as mitochondrial ATP, respiratory complex IV activity and quantity or oxygen consumption. Despite that, iPSC harbouring “common deletion” were able to differentiate into three germ layers. Besides, cybrids clones only showed mitochondrial dysfunction when heteroplasmy level reached 70%. Some differences observed among models may depend on their metabolic profile, therefore we consider these three models are useful for the in vitro study of the PS as well as for testing new specific therapies.