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

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…

• TM
  Tianjin Municipal Health Commission

  Award: 2024010
• NN
  National Natural Science Foundation of China

  Awards: 82074211, 82304896
• TU
  Tianjin University

  Award: 82074211
• NU
  Nanjing University of Chinese Medicine

  Award: YJSKC-20231016
• TM
  Tianjin Municipal Education Commission

  Award: 2022KJ149