We are pleased to announce that Prof. Bartosz Szczesny from The University of Texas Medical Branch, USA, will join Targeting Extracellular Vesicles 2026 as a speaker.

Mitochondrial dysfunction is a hallmark of various pathologies, yet the mechanisms linking this dysfunction to innate immune responses remain poorly understood. We demonstrate that chronic oxidative stress induces mitochondrial DNA (mtDNA) damage and its subsequent release from affected cells via extracellular vesicles (EVs). Sharing structural characteristics with bacterial DNA, this damaged mtDNA acts as a potent danger-associated molecular pattern (DAMP). Using cellular and animal models of lung, retina, and traumatic brain injuries, we established EVs-mediated mtDNA transfer as a critical mode of intercellular communication. Specifically, in traumatic brain injury, EVs mediate crosstalk between damaged neurons and microglia. Furthermore, we identified the cytoplasmic sensor Z-DNA binding protein 1 (ZBP1) as a key intracellular receptor for damaged mtDNA. Our findings position the mtDNA-ZBP1 axis as a previously unrecognized regulator of neuroinflammation and provide potential targets for mitigating immune-mediated tissue damage.