This title appears in the Scientific Report :
2021
Please use the identifier:
http://dx.doi.org/10.1016/j.cell.2020.02.044 in citations.
Please use the identifier: http://hdl.handle.net/2128/27108 in citations.
Aralar Sequesters GABA into Hyperactive Mitochondria, Causing Social Behavior Deficits
Aralar Sequesters GABA into Hyperactive Mitochondria, Causing Social Behavior Deficits
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 muta...
Saved in:
Personal Name(s): | Kanellopoulos, Alexandros K. |
---|---|
Mariano, Vittoria / Spinazzi, Marco / Woo, Young Jae / McLean, Colin / Pech, Ulrike / Li, Ka Wan / Armstrong, J. Douglas / Giangrande, Angela / Callaerts, Patrick / Smit, August B. / Abrahams, Brett S. / Fiala, Andre / Achsel, Tilmann / Bagni, Claudia (Corresponding author) | |
Contributing Institute: |
Computational Biomedicine; IAS-5 Computational Biomedicine; INM-9 |
Published in: | Cell, 180 (2020) 6, S. 1178 - 1197.e20 |
Imprint: |
New York, NY
Elsevier
2020
|
DOI: |
10.1016/j.cell.2020.02.044 |
Document Type: |
Journal Article |
Research Program: |
Theory, modelling and simulation |
Link: |
Published on 2020-03-19. Available in OpenAccess from 2021-03-19. |
Publikationsportal JuSER |
Please use the identifier: http://hdl.handle.net/2128/27108 in citations.
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. |