AUTHOR=Bjerregaard Victoria A. , Schönewolf-Greulich Bitten , Juel Rasmussen Lene , Desler Claus , Tümer Zeynep 

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

JOURNAL=Frontiers in Neurology

VOLUME=11

YEAR=2020

URL=https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2020.00163

DOI=10.3389/fneur.2020.00163

ISSN=1664-2295

ABSTRACT=<p><bold>Background:</bold> 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 (<italic>IMMP2L</italic>) 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 <italic>IMMP2L</italic> deletions and compared with GTS without <italic>IMMP2L</italic> deletions and healthy controls.</p><p><bold>Methods:</bold> Mitochondrial function in fibroblasts from GTS patients and non-GTS parents (with and without <italic>IMMP2L</italic> 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.</p><p><bold>Results:</bold> None of the mitochondrial parameters assessed in this study were significantly distinctive when comparing GTS patients with and without <italic>IMMP2L</italic> deletions against healthy controls or parents with or without <italic>IMMP2L</italic> deletions, and we did not observe altered cell programming.</p><p><bold>Conclusion:</bold> This study suggests that <italic>IMMP2L</italic> 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 <italic>IMMP2L</italic> variants affect mitochondrial function during specific instances of stress stimuli or in brain regions suggested to be affected in GTS.</p>