title: Impaired Mitochondrial Function and Dynamics in the Pathogenesis of FXTAS.
abstract: 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.
authors: Biochemistry and Molecular Genetics Department, Hospital Clinic, C/Villarroel 170, 08036, Barcelona, Spain.|CIBER of rare diseases (CIBERER) and IDIBAPS, Villarroel 170, 08036, Barcelona, Spain.
authors: M I
authors: MI
authors: Alvarez-Mora
authors: Biochemistry and Molecular Genetics Department, Hospital Clinic, C/Villarroel 170, 08036, Barcelona, Spain.|CIBER of rare diseases (CIBERER) and IDIBAPS, Villarroel 170, 08036, Barcelona, Spain.
authors: L
authors: L
authors: Rodriguez-Revenga
authors: Biochemistry and Molecular Genetics Department, Hospital Clinic, C/Villarroel 170, 08036, Barcelona, Spain.|CIBER of rare diseases (CIBERER) and IDIBAPS, Villarroel 170, 08036, Barcelona, Spain.
authors: I
authors: I
authors: Madrigal
authors: CIBER of rare diseases (CIBERER) and IDIBAPS, Villarroel 170, 08036, Barcelona, Spain.|Muscle Research and Mitochondrial Function Laboratory, CELLEX, Faculty of Medicine-University of Barcelona, Internal Medicine Department, Hospital Clinic, Villarroel 170, 08036, Barcelona, Spain.
authors: M
authors: M
authors: Guitart-Mampel
authors: CIBER of rare diseases (CIBERER) and IDIBAPS, Villarroel 170, 08036, Barcelona, Spain.|Muscle Research and Mitochondrial Function Laboratory, CELLEX, Faculty of Medicine-University of Barcelona, Internal Medicine Department, Hospital Clinic, Villarroel 170, 08036, Barcelona, Spain.
authors: G
authors: G
authors: Garrabou
authors: Biochemistry and Molecular Genetics Department, Hospital Clinic, C/Villarroel 170, 08036, Barcelona, Spain. mmila@clinic.ub.es.|CIBER of rare diseases (CIBERER) and IDIBAPS, Villarroel 170, 08036, Barcelona, Spain. mmila@clinic.ub.es.
authors: M
authors: M
authors: Milà
mesh_terms: D001259:Ataxia / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005347:Fibroblasts / Q000473:pathology / Q000502:physiology; D005600:Fragile X Syndrome / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000473:pathology / Q000502:physiology; D008297:Male; D008928:Mitochondria / Q000473:pathology / Q000502:physiology*; D014202:Tremor / Q000378:metabolism* / Q000473:pathology
keywords: FXTAS; Mitochondrial dynamics; Mitochondrial dysfunction; Oxygen uptake; ROS production