Journal Article

FZJ-2021-00927

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Aralar Sequesters GABA into Hyperactive Mitochondria, Causing Social Behavior Deficits

Kanellopoulos, A. K. ; Mariano, V. ; Spinazzi, M. ; Woo, Y. J. ; McLean, C. ; Pech, U. ; Li, K. W. ; Armstrong, J. D.FZJ* ; Giangrande, A. ; Callaerts, P. ; Smit, A. B. ; Abrahams, B. S. ; Fiala, A. ; Achsel, T. ; Bagni, C. (Corresponding author)

2020
Elsevier New York, NY

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Please use a persistent id in citations: http://hdl.handle.net/2128/27108  doi:10.1016/j.cell.2020.02.044

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.

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Contributing Institute(s):

1. Computational Biomedicine (INM-9)
2. Computational Biomedicine (IAS-5)

Research Program(s):

1. 574 - Theory, modelling and simulation (POF3-574) (POF3-574)

Appears in the scientific report 2021

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Database coverage:
; ; ; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; Ebsco Academic Search ; Essential Science Indicators ; Nationallizenz ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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