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

• Published in: Frontiers in neurology 2020-03, Vol.11, p.163-163
• Main Authors: Bjerregaard, Victoria A, Schönewolf-Greulich, Bitten, Juel Rasmussen, Lene, Desler, Claus, Tümer, Zeynep
• Format: Article
• Language: English
• Subjects: Gilles de la Tourette syndrome; GTS; IMMP2L; mitochondria; Neurology; oxidative stress
• ISSN: 1664-2295; 1664-2295
• DOI: 10.3389/fneur.2020.00163

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