Regulation of blood-brain barrier integrity by <i>Dmp1</i> -expressing astrocytes through mitochondrial transfer
Delin Liu, Peng Liao, Hao Li, Sihan Tong, Bingqi Wang, Yafei Lu, Youshui Gao, Yigang Huang, Hao Zhou, Linjing Shi, J. M. Papadimitriou, Zong Yao, Jun Yuan, Peilin Chen, Ziming Chen, Peng Ding, Yongqiang Zheng, Changqing Zhang, Minghao Zheng, Junjie Gao
Abstract
The blood-brain barrier (BBB) acts as the crucial physical filtration structure in the central nervous system. Here, we investigate the role of a specific subset of astrocytes in the regulation of BBB integrity. We showed that Dmp1- expressing astrocytes transfer mitochondria to endothelial cells via their endfeet for maintaining BBB integrity. Deletion of the Mitofusin 2 ( Mfn2 ) gene in Dmp1 -expressing astrocytes inhibited the mitochondrial transfer and caused BBB leakage. In addition, the decrease of MFN2 in astrocytes contributes to the age-associated reduction of mitochondrial transfer efficiency and thus compromises the integrity of BBB. Together, we describe a mechanism in which astrocytes regulate BBB integrity through mitochondrial transfer. Our findings provide innnovative insights into the cellular framework that underpins the progressive breakdown of BBB associated with aging and disease.