Aralar Sequesters GABA into Hyperactive Mitochondria, Causing Social Behavior Deficits
| Autor: | André Fiala, Brett S. Abrahams, J. Douglas Armstrong, August B. Smit, Colin Mclean, Young Jae Woo, Claudia Bagni, Angela Giangrande, Tilmann Achsel, Marco Spinazzi, Ka Wan Li, Ulrike Pech, Patrick Callaerts, Alexandros K. Kanellopoulos, Vittoria Mariano |
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| Přispěvatelé: | Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Amsterdam Neuroscience - Cellular & Molecular Mechanisms, AIMMS, Molecular and Cellular Neurobiology, Center for Neurogenomics and Cognitive Research |
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Male
[SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology Mutant Mitochondrion mitochondrial activity Mitochondrial Membrane Transport Proteins Synaptic Transmission Animals Genetically Modified GABA 0302 clinical medicine Drosophila Proteins Homeostasis BRAIN gamma-Aminobutyric Acid ComputingMilieux_MISCELLANEOUS GENE-EXPRESSION Neurons 0303 health sciences Neurodevelopmental disorders Settore BIO/13 Research Highlight Mitochondria DROSOPHILA Drosophila melanogaster Schizophrenia GABAergic [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC] Drosophila COMPLEX I Life Sciences & Biomedicine FRAGILE-X medicine.drug Aralar Biochemistry & Molecular Biology social group behavior autism Biology Neurotransmission Molecular neuroscience General Biochemistry Genetics and Molecular Biology gamma-Aminobutyric acid Mitochondrial Proteins PROTEIN COMPLEXES CYFIP1 03 medical and health sciences mitochondrial membrane potential SLC25A12 (AGC1) medicine Animals Humans ddc:610 Social Behavior 030304 developmental biology Adaptor Proteins Signal Transducing Aspartic Acid Science & Technology AUTISM SPECTRUM DISORDER Calcium-Binding Proteins Transporter Cell Biology medicine.disease DYSFUNCTION schizophrenia Glucose Calcium Neuroscience 030217 neurology & neurosurgery |
| Zdroj: | Kanellopoulos, A K, Mariano, V, Spinazzi, M, Woo, Y J, McLean, C, Pech, U, Li, K W, Armstrong, J D, Giangrande, A, Callaerts, P, Smit, A B, Abrahams, B S, Fiala, A, Achsel, T & Bagni, C 2020, ' Aralar Sequesters GABA into Hyperactive Mitochondria, Causing Social Behavior Deficits ', Cell, vol. 180, no. 6, e20, pp. 1178-1197 . https://doi.org/10.1016/j.cell.2020.02.044 Cell Cell, Elsevier, 2020, 180 (6), pp.1178-1197.e20. ⟨10.1016/j.cell.2020.02.044⟩ Cell, 180(6), 1178-1197.e20. Cell Press Kanellopoulos, A K, Mariano, V, Spinazzi, M, Woo, Y J, McLean, C, Pech, U, Li, K W, Armstrong, J D, Giangrande, A, Callaerts, P, Smit, A B, Abrahams, B S, Fiala, A, Achsel, T & Bagni, C 2020, ' Aralar Sequesters GABA into Hyperactive Mitochondria, Causing Social Behavior Deficits ', Cell, vol. 180, no. 6, pp. 1178-1197.e20 . https://doi.org/10.1016/j.cell.2020.02.044 Cell 180(6), 1178-1197.e20 (2020). doi:10.1016/j.cell.2020.02.044 Signal Transduction and Targeted Therapy |
| ISSN: | 0092-8674 1097-4172 |
| Popis: | Social impairment is frequently associated with mitochondrial dysfunction and altered neurotransmission. Although mitochondrial function is crucial for brain homeostasis, it remains unknown whether mitochondrial disruption contributes to social behavioral deficits. Here, we show that Drosophila mutants in the homolog of the human CYFIP1, a gene linked to autism and schizophrenia, exhibit mitochondrial hyperactivity and altered group behavior. We identify the regulation of GABA availability by mitochondrial activity as a biologically relevant mechanism and demonstrate its contribution to social behavior. Specifically, increased mitochondrial activity causes gamma aminobutyric acid (GABA) sequestration in the mitochondria, reducing GABAergic signaling and resulting in social deficits. Pharmacological and genetic manipulation of mitochondrial activity or GABA signaling corrects the observed abnormalities. We identify Aralar as the mitochondrial transporter that sequesters GABA upon increased mitochondrial activity. This study increases our understanding of how mitochondria modulate neuronal homeostasis and social behavior under physiopathological conditions. ispartof: CELL vol:180 issue:6 pages:1178-+ ispartof: location:United States status: published |
| Databáze: | OpenAIRE |
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