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.
journal_name
Celljournal_title
Cellauthors
Kanellopoulos AK,Mariano V,Spinazzi M,Woo YJ,McLean C,Pech U,Li KW,Armstrong JD,Giangrande A,Callaerts P,Smit AB,Abrahams BS,Fiala A,Achsel T,Bagni Cdoi
10.1016/j.cell.2020.02.044subject
Has Abstractpub_date
2020-03-19 00:00:00pages
1178-1197.e20issue
6eissn
0092-8674issn
1097-4172pii
S0092-8674(20)30221-Xjournal_volume
180pub_type
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