Mitochondrial morphology is associated with respiratory chain uncoupling in autism spectrum disorder
| Autor: | Loïc Lionnard, Marie Tippett, Richard E. Frye, Abdel Aouacheria, Mathilde Fréchet, Karima Kissa, Leanna Delhey, Indrapal N. Singh, Amrit Ammanamanchi, Hanane Chajra, Patrick John McCarty, Shannon Rose, Mohammad A. Karim, Victor Racine |
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| Přispěvatelé: | Phoenix Children's Hospital, Institut des Sciences de l'Evolution de Montpellier (UMR ISEM), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université de Montpellier (UM)-Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Centre National de la Recherche Scientifique (CNRS)-Institut de recherche pour le développement [IRD] : UR226, Clariant Active ingredients, LPHI - Laboratory of Pathogen Host Interactions (LPHI), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), QuantaCell SAS, Arkansas Children's Research Institute, Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université de Montpellier (UM)-Institut de recherche pour le développement [IRD] : UR226-Centre National de la Recherche Scientifique (CNRS), Laboratory of Pathogen Host Interactions [Montpellier] (LPHI) |
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
medicine.medical_specialty
Autism Spectrum Disorder Physiology [SDV]Life Sciences [q-bio] Respiratory chain Neurosciences. Biological psychiatry. Neuropsychiatry [SDV.BC]Life Sciences [q-bio]/Cellular Biology Biology Molecular neuroscience Article Electron Transport 03 medical and health sciences Cellular and Molecular Neuroscience Social Responsiveness Scale 0302 clinical medicine Neurodevelopmental disorder Internal medicine Respiration mental disorders medicine Humans Fibroblast Trial registration Biological Psychiatry 030304 developmental biology 0303 health sciences Electron Transport Complex I medicine.disease Mitochondrial morphology Mitochondria Psychiatry and Mental health Endocrinology medicine.anatomical_structure Autism spectrum disorder Oxidation-Reduction 030217 neurology & neurosurgery RC321-571 |
| Zdroj: | Translational Psychiatry Translational Psychiatry, Nature Pub. Group, 2021, 11 (1), pp.527. ⟨10.1038/s41398-021-01647-6⟩ Translational Psychiatry, 2021, 11 (1), pp.527. ⟨10.1038/s41398-021-01647-6⟩ Translational Psychiatry, Vol 11, Iss 1, Pp 1-17 (2021) |
| ISSN: | 2158-3188 |
| Popis: | Autism spectrum disorder (ASD) is a neurodevelopmental disorder that is associated with unique changes in mitochondrial metabolism, including elevated respiration rates and morphological alterations. We examined electron transport chain (ETC) complex activity in fibroblasts derived from 18 children with ASD as well as mitochondrial morphology measurements in fibroblasts derived from the ASD participants and four typically developing controls. In ASD participants, symptoms severity was measured by the Social Responsiveness Scale and Aberrant Behavior Checklist. Mixed-model regression demonstrated that alterations in mitochondrial morphology were associated with both ETC Complex I+III and IV activity as well as the difference between ETC Complex I+III and IV activity. The subgroup of ASD participants with relative elevation in Complex IV activity demonstrated more typical mitochondrial morphology and milder ASD related symptoms. This study is limited by sample size given the invasive nature of obtaining fibroblasts from children. Furthermore, since mitochondrial function is heterogenous across tissues, the result may be specific to fibroblast respiration. Previous studies have separately described elevated ETC Complex IV activity and changes in mitochondrial morphology in cells derived from children with ASD but this is the first study to link these two findings in mitochondrial metabolism. The association between a difference in ETC complex I+III and IV activity and normal morphology suggests that mitochondrial in individuals with ASD may require ETC uncoupling to function optimally. Further studies should assess the molecular mechanisms behind these unique metabolic changes.Trial registration: Protocols used in this study were registered in clinicaltrials.gov as NCT02000284 and NCT02003170. |
| Databáze: | OpenAIRE |
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