Mitochondrial Function in Gilles de la Tourette Syndrome Patients With and Without Intragenic IMMP2L Deletions

Abstract

<b>Background:</b> Gilles de la Tourette syndrome (GTS) is a neurodevelopmental condition characterized by motor and vocal tics. The underlying etiology remains largely unknown, and GTS is considered as a complex multifactorial disorder associated with effects of several genes in combination with environmental factors. The inner mitochondrial membrane peptidase, subunit 2 (<i>IMMP2L</i>) has been suggested as one of the susceptibility genes for GTS, and IMMP2L-deficient mouse and human cells show increased levels of mitochondrial oxidative stress and altered cell fate programming. Hence, a potential involvement of IMMP2L-induced mitochondrial dysfunction in GTS pathology is yet to be elucidated. To address this, we investigated mitochondrial function in a group of GTS patients with intragenic <i>IMMP2L</i> deletions and compared with GTS without <i>IMMP2L</i> deletions and healthy controls. <b>Methods:</b> Mitochondrial function in fibroblasts from GTS patients and non-GTS parents (with and without <i>IMMP2L</i> deletions) compared to healthy controls were evaluated by measuring mitochondrial superoxide production, mitochondrial membrane potential, mitochondrial mass, and mitochondrial respiration. In addition, we evaluated apoptosis and senescence. <b>Results:</b> None of the mitochondrial parameters assessed in this study were significantly distinctive when comparing GTS patients with and without <i>IMMP2L</i> deletions against healthy controls or parents with or without <i>IMMP2L</i> deletions, and we did not observe altered cell programming. <b>Conclusion:</b> This study suggests that <i>IMMP2L</i> deletions do not lead to a substantial general mitochondrial dysfunction in GTS fibroblasts. Assessing a large cohort of controls and patients of similar age and gender would possibly reveal small differences in mitochondrial function. However, it is possible that <i>IMMP2L</i> variants affect mitochondrial function during specific instances of stress stimuli or in brain regions suggested to be affected in GTS.