Mitochondrial dysfunction in microglia: a novel perspective of depression pathogenesis.
6 affiliations
- 1Department of Rehabilitation Medicine, Putuo People's Hospital, School of Medicine, Tongji University, Shanghai, 200060, China.
- 2Center for Translational Neurodegeneration and Regenerative Therapy, Yangzhi Rehabilitation Hospital, School of Medicine, Tongji University, Shanghai, 200065, China. [email protected].
- 3Department of Rehabilitation Medicine, Putuo People's Hospital, School of Medicine, Tongji University, Shanghai, 200060, China. [email protected].
- 4Shanghai Key Laboratory of Anesthesiology and Brain Functional Modulation, Clinical Research Center for Anesthesiology and Perioperative Medicine, Shanghai Fourth People's Hospital, School of Medicine, Tongji University, Shanghai, 200434, China. [email protected].
- 5State Key Laboratory of Cardiology and Medical Innovation Center, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, 200123, China. [email protected].
- 6Innovation Center of Medical Basic Research for Brain Aging and Associated Diseases, Ministry of Education, Tongji University, Shanghai, 200221, China. [email protected].
Abstract
Major depressive disorder is a prevalent psychiatric disease that is closely linked to chronic low-grade neuroinflammation, which is primarily driven by microglia, the primary resident immune cells in the brain. Accumulating studies started to reveal that mitochondria, the powerhouses of the cell, play an important role in microglia-mediated neuroinflammation and neurotoxicity in depression. Stress-induced mitochondrial dysfunction triggers microglial activation through distinct mechanisms including energy metabolism patterns transition, electron transport chain impairment, reactive oxygen species accumulation, mitochondrial DNA damage, imbalanced fission and fusion, autophagy, and mitophagy deficiency, which cause the onset and progression of depression. In this review, we described microglial activation in animal models and clinically depressed patients, summarized current understanding of mitochondrial dysfunction-mediated microglial activation, and emphasized the possible mechanisms by which microglial mitochondrial dysfunction participates in the pathogenesis of depression. Understanding the roles and underlying mechanisms of mitochondrial dysfunction in neuroinflammation and neurotoxicity in depression may shed light on developing novel therapeutic strategies to fight against this devastating mental illness.
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BibTeX
@article{jia2026mitochondrial,
title = {{Mitochondrial dysfunction in microglia: a novel perspective of depression pathogenesis.}},
author = {Yishu Jia and Shuyu Zhao and Feier Miao and Zihan Yang and Shiyi Zhao and Qinfeng Wu and Yi Wang and Xiaohuan Xia},
journal = {Inflammation and regeneration},
year = {2026},
month = oct,
doi = {10.1186/s41232-026-00444-2},
url = {https://europepmc.org/article/MED/42919365},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Mitochondrial dysfunction in microglia: a novel perspective of depression pathogenesis.
AU - Yishu Jia
AU - Shuyu Zhao
AU - Feier Miao
AU - Zihan Yang
AU - Shiyi Zhao
AU - Qinfeng Wu
AU - Yi Wang
AU - Xiaohuan Xia
PY - 2026
DA - 2026/10/22
JO - Inflammation and regeneration
DO - 10.1186/s41232-026-00444-2
UR - https://europepmc.org/article/MED/42919365
AB - Major depressive disorder is a prevalent psychiatric disease that is closely linked to chronic low-grade neuroinflammation, which is primarily driven by microglia, the primary resident immune cells in the brain. Accumulating studies started to reveal that mitochondria, the powerhouses of the cell, play an important role in microglia-mediated neuroinflammation and neurotoxicity in depression. Stress-induced mitochondrial dysfunction triggers microglial activation through distinct mechanisms including energy metabolism patterns transition, electron transport chain impairment, reactive oxygen species accumulation, mitochondrial DNA damage, imbalanced fission and fusion, autophagy, and mitophagy deficiency, which cause the onset and progression of depression. In this review, we described microglial activation in animal models and clinically depressed patients, summarized current understanding of mitochondrial dysfunction-mediated microglial activation, and emphasized the possible mechanisms by which microglial mitochondrial dysfunction participates in the pathogenesis of depression. Understanding the roles and underlying mechanisms of mitochondrial dysfunction in neuroinflammation and neurotoxicity in depression may shed light on developing novel therapeutic strategies to fight against this devastating mental illness.
SN - 1880-9693
SN - 1880-8190
ER -