Aralar Sequesters GABA into Hyperactive Mitochondria, Causing Social Behavior Deficits.
Details
Serval ID
serval:BIB_07089D1B525D
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Aralar Sequesters GABA into Hyperactive Mitochondria, Causing Social Behavior Deficits.
Journal
Cell
ISSN
1097-4172 (Electronic)
ISSN-L
0092-8674
Publication state
Published
Issued date
19/03/2020
Peer-reviewed
Oui
Volume
180
Number
6
Pages
1178-1197.e20
Language
english
Notes
Publication types: Journal Article
Publication Status: ppublish
Publication Status: ppublish
Abstract
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.
Keywords
Aralar, CYFIP1, Drosophila, GABA, SLC25A12 (AGC1), autism, mitochondrial activity, mitochondrial membrane potential, schizophrenia, social group behavior
Pubmed
Create date
01/04/2020 19:18
Last modification date
01/11/2020 6:23