Research progress on mitochondrial DNA release mechanism and its induction of inflammatory responses
HAO Shuang
ZHOU Jiaheng
QU Shaochen
WU Guiling
AN Jiong
ZHANG Pengfei
LI Jia
YANG Hongyan
Abstract：Mitochondria are important organelles responsible for regulating various life processes such as tricarboxylic acid cycle,calcium balance,cell apoptosis,cell death,cell cycle,and inflammation.Unlike other organelles,mitochondria contain a small amount of mitochondrial DNA(mtDNA),which is uniformly distributed in the mitochondrial matrix in a quasi-nuclear form under normal circumstances,and thus maintains mitochondrial homeostasis.When cells are under stress conditions such as senescence,apoptosis,metabolic disorders,and hypoxia,however,mitochondrial function becomes abnormal.In this case,mtDNA is released into the cytoplasm through mitochondrial membrane permeability transition pores,Bax/Bcl-2 homologous antagonist/killer(Bak)macropores or discharged into the extracellular space through various pathways such as tunneling nanotubes,extracellular vesicles,migrasome,and connexin.Once mtDNA is released from mitochondria into the cytoplasm or extracellular environment,it will activate Toll-like receptor 9,nucleotide-binding oligomerization domain-like receptor family pyrin domain containing 3 inflammasomes,cyclic GMP/AMP synthase-interferon genes signaling pathways,promoting the release of inflammatory cytokines,inducing inflammatory responses,and participating in the occurrence and development of various diseases such as aging and Alzheimer's disease.
Keywords：mitochondriamitochondrial DNAnuclear DNAinflammation
Publication Date：2025-01-27
Online Publishing Date：2026-08-26(First online date of this platform, not the publication date of the document)