Regulation of blood-brain barrier integrity by Dmp1-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; John Papadimitriou; Yao Zong; Jun Yuan; Peilin Chen; Ziming Chen; Peng Ding; Yongqiang Zheng; Changqing Zhang; Minghao Zheng; Junjie Gao

doi:10.1126/sciadv.adk2913

Regulation of blood-brain barrier integrity by Dmp1-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, John Papadimitriou, Yao Zong, Jun Yuan, Peilin Chen, Ziming Chen, Peng Ding, Yongqiang Zheng, Changqing Zhang, Minghao Zheng, Junjie Gao

Research output: Contribution to journal › Article › peer-review

4 Citations (Scopus)

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.

Original language	English
Article number	eadk2913
Number of pages	19
Journal	Science Advances
Volume	10
Issue number	26
DOIs	https://doi.org/10.1126/sciadv.adk2913
Publication status	Published - 28 Jun 2024

Access to Document

10.1126/sciadv.adk2913Licence: CC BY-NC

Cite this

Liu, D., Liao, P., Li, H., Tong, S., Wang, B., Lu, Y., Gao, Y., Huang, Y., Zhou, H., Shi, L., Papadimitriou, J., Zong, Y., Yuan, J., Chen, P., Chen, Z., Ding, P., Zheng, Y., Zhang, C., Zheng, M., & Gao, J. (2024). Regulation of blood-brain barrier integrity by Dmp1-expressing astrocytes through mitochondrial transfer. Science Advances, 10(26), Article eadk2913. https://doi.org/10.1126/sciadv.adk2913

@article{7b59d32be47b4691aca0cc10aacb3d5a,

title = "Regulation of blood-brain barrier integrity by Dmp1-expressing astrocytes through mitochondrial transfer",

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.",

author = "Delin Liu and Peng Liao and Hao Li and Sihan Tong and Bingqi Wang and Yafei Lu and Youshui Gao and Yigang Huang and Hao Zhou and Linjing Shi and John Papadimitriou and Yao Zong and Jun Yuan and Peilin Chen and Ziming Chen and Peng Ding and Yongqiang Zheng and Changqing Zhang and Minghao Zheng and Junjie Gao",

year = "2024",

month = jun,

day = "28",

doi = "10.1126/sciadv.adk2913",

language = "English",

volume = "10",

journal = "Science Advances",

issn = "2375-2548",

publisher = "AMER ASSOC ADVANCEMENT SCIENCE",

number = "26",

}

Liu, D, Liao, P, Li, H, Tong, S, Wang, B, Lu, Y, Gao, Y, Huang, Y, Zhou, H, Shi, L, Papadimitriou, J, Zong, Y, Yuan, J , Chen, P, Chen, Z, Ding, P, Zheng, Y, Zhang, C, Zheng, M & Gao, J 2024, 'Regulation of blood-brain barrier integrity by Dmp1-expressing astrocytes through mitochondrial transfer', Science Advances, vol. 10, no. 26, eadk2913. https://doi.org/10.1126/sciadv.adk2913

TY - JOUR

T1 - Regulation of blood-brain barrier integrity by Dmp1-expressing astrocytes through mitochondrial transfer

AU - Liu, Delin

AU - Liao, Peng

AU - Li, Hao

AU - Tong, Sihan

AU - Wang, Bingqi

AU - Lu, Yafei

AU - Gao, Youshui

AU - Huang, Yigang

AU - Zhou, Hao

AU - Shi, Linjing

AU - Papadimitriou, John

AU - Zong, Yao

AU - Yuan, Jun

AU - Chen, Peilin

AU - Chen, Ziming

AU - Ding, Peng

AU - Zheng, Yongqiang

AU - Zhang, Changqing

AU - Zheng, Minghao

AU - Gao, Junjie

PY - 2024/6/28

Y1 - 2024/6/28

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85197143276&partnerID=8YFLogxK

U2 - 10.1126/sciadv.adk2913

DO - 10.1126/sciadv.adk2913

M3 - Article

C2 - 38941455

AN - SCOPUS:85197143276

SN - 2375-2548

VL - 10

JO - Science Advances

JF - Science Advances

IS - 26

M1 - eadk2913

ER -

Regulation of blood-brain barrier integrity by Dmp1-expressing astrocytes through mitochondrial transfer

Abstract

Access to Document

Other files and links

Fingerprint

Cite this