Crosstalk Between Mitochondrial DNA and Immune Response: Focus on Autism Spectrum Disorder

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by multiple dysfunctions in behavior, the nervous system, and the immune system. Increasing evidence suggests that mitochondrial DNA (mtDNA) plays a crucial role in the pathology of ASD. In clinical practice, altered mtDNA levels have been observed in various tissues of individuals with ASD. Mutation or oxidation of mtDNA is also closely related to the immune response associated with the pathology of autism. With mtDNA identified as a causal factor, much interest has focused on how its production affects neurodevelopment and neurophysiology. Here, we review how mtDNA leads to dysfunction of cellular mitochondria and immune response. We also illustrate the relationship between mtDNA alterations and the pathology of autism. Finally, we discuss the existing evidence on cell-free mtDNA associated with ASD and look forward to its application in clinical diagnosis and treatment.Graphical AbstractmtDNA[FCA1] dysfunctions detected in ASD, such as copy number variations, mutations, haplogroups, and heteroplasmies, may be critical contributors to neuroinflammation and behavioral issues. Released mtDNA triggers innate immune pathways. This process includes the activation of the TLR9, NLRP3, and cGAS-STING pathways. The process leads to the release of pro-inflammatory cytokines, further promoting immune response [FCA1]LE: Please be informed that the image contains cut-off data.