Mitochondrial DNA release and sensing in innate immune responses.
Jordyn J VanPortflietCole ChuteYuanjiu LeiTimothy E ShuttAndrew Phillip WestPublished in: Human molecular genetics (2024)
Mitochondria are pleiotropic organelles central to an array of cellular pathways including metabolism, signal transduction, and programmed cell death. Mitochondria are also key drivers of mammalian immune responses, functioning as scaffolds for innate immune signaling, governing metabolic switches required for immune cell activation, and releasing agonists that promote inflammation. Mitochondrial DNA (mtDNA) is a potent immunostimulatory agonist, triggering pro-inflammatory and type I interferon responses in a host of mammalian cell types. Here we review recent advances in how mtDNA is detected by nucleic acid sensors of the innate immune system upon release into the cytoplasm and extracellular space. We also discuss how the interplay between mtDNA release and sensing impacts cellular innate immune endpoints relevant to health and disease.
Keyphrases
- innate immune
- mitochondrial dna
- copy number
- immune response
- nucleic acid
- cell death
- public health
- single cell
- oxidative stress
- reactive oxygen species
- high resolution
- mental health
- genome wide
- endoplasmic reticulum
- toll like receptor
- stem cells
- dna methylation
- health information
- tissue engineering
- low cost
- anti inflammatory
- human health
- inflammatory response
- high density