Mitochondrial involvement plays an important role in neurodegenerative diseases. At least one-third of adult carriers of a FMR1 premutation (55-200 CGG repeats) are at risk of presenting an adult-onset neurodegenerative disorder known as fragile X-associated tremor/ataxia syndrome (FXTAS). In an attempt to provide new insights into the mechanisms involved in the pathogenesis of FXTAS, we characterized mitochondrial function and dynamics by the assessment of oxidative respiratory chain function, mitochondrial content, oxidative stress levels, and mitochondrial network complexity. Regarding mitochondrial function, we found that mitochondrial respiratory capacity is compromised in skin fibroblasts whereas in blood, no differences were observed between the FXTAS and control groups. Furthermore, fibroblasts from FXTAS patients presented altered mitochondrial architecture, with more circular and less interconnected mitochondria being observed. Mitochondrial function and dynamics deregulation and characteristic of neurological disorders are present in FXTAS patients. These features might be limiting temporal and spatial bioenergetics cells supply and thus contributing to disease pathogenesis.
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This work was supported by the Instituto de Salud Carlos III (PI12/00879), co-financed by Fondo Europeo de Desarrollo Regional (FEDER) “una manera de hacer Europa” and AGAUR from the Autonomous Catalan Government (2014 SGR603). The CIBER de Enfermedades Raras is an initiative of the Instituto de Salud Carlos III. We wish to thank the FXTAS patients and FXS families for their cooperation as well as Marc Catalan and Esther Tobias from Cellex and IDIBAPS (Barcelona, Spain) for their contribution in this work.
Conflict of Interest Statement
All authors have read the journal’s policy on conflicts of interest. The authors declare no conflict of interest.
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Alvarez-Mora, M.I., Rodriguez-Revenga, L., Madrigal, I. et al. Impaired Mitochondrial Function and Dynamics in the Pathogenesis of FXTAS. Mol Neurobiol 54, 6896–6902 (2017). https://doi.org/10.1007/s12035-016-0194-7
- Oxygen uptake
- ROS production
- Mitochondrial dynamics
- Mitochondrial dysfunction