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Review
. 2025 May;62(5):5629-5639.
doi: 10.1007/s12035-024-04637-z. Epub 2024 Nov 26.

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

Wenxuan Qu  1 , Ge Yan  1 , Yajuan Du  1 , Xinyang Zhou  1 , Chutian Huang  1 , Bei Li  1 , Junmei Zhou  1 , Qian Li  2
Affiliations
Review

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

Wenxuan Qu et al. Mol Neurobiol. 2025 May.

Abstract

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.

Keywords: Autism spectrum disorder; Maternal immune activation; Microglia; Mitochondrial DNA; Neuroinflammation.

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Conflict of interest statement

Declarations. Conflict of Interest: The authors state that the present manuscript presents no conflicts of interest.

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