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Publications

Journal Article Review Epublish 32 citations

PubMed: 39920753 DOI: 10.1186/s12974-025-03363-0

Mitochondrial DNA leakage: underlying mechanisms and therapeutic implications in neurological disorders.

J Neuroinflammation 22(1):34

Authors: Guangming Zhang, Huayuan Wei, Anliu Zhao, Xu Yan, Xiaolu Zhang, Jiali Gan, Maojuan Guo, Jie Wang, Fayan Zhang, Yifang Jiang, Xinxing Liu, Zhen Yang, Xijuan Jiang

Affiliations

  • School of Integrative Medicine, Tianjin University of Traditional Chinese Medicine, No. 10, Poyang Lake Road, Tuanbo New City West District, Jinghai District, Tianjin, 301617, China.
  • Heart Disease Department, Tianjin Academy of Traditional Chinese Medicine Affiliated Hospital, Tianjin, China.
  • School of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, China.
  • School of Chinese Materia Medica, Tianjin University of Traditional Chinese Medicine, No. 10, Poyang Lake Road, Tuanbo New City West District, Jinghai District, Tianjin, China. Tianjin Key Laboratory of Therapeutic Substance of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, No. 10, Poyang Lake Road, Tuanbo New City West District, Jinghai District, Tianjin, China.
  • School of Integrative Medicine, Tianjin University of Traditional Chinese Medicine, No. 10, Poyang Lake Road, Tuanbo New City West District, Jinghai District, Tianjin, 301617, China.

Abstract

Mitochondrial dysfunction is a pivotal instigator of neuroinflammation, with mitochondrial DNA (mtDNA) leakage as a critical intermediary. This review delineates the intricate pathways leading to mtDNA release, which include membrane permeabilization, vesicular trafficking, disruption of homeostatic regulation, and abnormalities in mitochondrial dynamics. The escaped mtDNA activates cytosolic DNA sensors, especially cyclic gmp-amp synthase (cGAS) signalling and inflammasome, initiating neuroinflammatory cascades via pathways, exacerbating a spectrum of neurological pathologies. The therapeutic promise of targeting mtDNA leakage is discussed in detail, underscoring the necessity for a multifaceted strategy that encompasses the preservation of mtDNA homeostasis, prevention of membrane leakage, reestablishment of mitochondrial dynamics, and inhibition the activation of cytosolic DNA sensors. Advancing our understanding of the complex interplay between mtDNA leakage and neuroinflammation is imperative for developing precision therapeutic interventions for neurological disorders.

MeSH

Mitochondrial Dynamics, Dna, Mitochondrial, Therapeutics, Nervous System Diseases, Dna, Membranes

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