近日,瑞士洛桑大学Claudia Bagni研究组发现,Aralar将GABA隔离进过度活跃的线粒体,从而导致社交行为缺陷。相关论文发表在2020年3月19日出版的《细胞》杂志上。
Author: Alexandros K. Kanellopoulos, Vittoria Mariano, Marco Spinazzi, Young Jae Woo, Colin McLean, Ulrike Pech, Ka Wan Li, J. Douglas Armstrong, Angela Giangrande, Patrick Callaerts, August B. Smit, Brett S. Abrahams, Andre Fiala, Tilmann Achsel, Claudia Bagni
Issue&Volume: 2020/03/19
Abstract: Social impairment is frequently associated with mitochondrial dysfunction and alteredneurotransmission. Although mitochondrial function is crucial for brain homeostasis,it remains unknown whether mitochondrial disruption contributes to social behavioraldeficits. Here, we show that Drosophila mutants in the homolog of the human CYFIP1, a gene linked to autism and schizophrenia, exhibit mitochondrial hyperactivity andaltered group behavior. We identify the regulation of GABA availability by mitochondrialactivity as a biologically relevant mechanism and demonstrate its contribution tosocial behavior. Specifically, increased mitochondrial activity causes gamma aminobutyricacid (GABA) sequestration in the mitochondria, reducing GABAergic signaling and resultingin social deficits. Pharmacological and genetic manipulation of mitochondrial activityor GABA signaling corrects the observed abnormalities. We identify Aralar as the mitochondrialtransporter that sequesters GABA upon increased mitochondrial activity. This studyincreases our understanding of how mitochondria modulate neuronal homeostasis andsocial behavior under physiopathological conditions.
DOI: 10.1016/j.cell.2020.02.044
Source: https://www.cell.com/cell/fulltext/S0092-8674(20)30221-X