Chlorine wrecks lung epithelium and endothelium. Dubey, Crossman and Matalon already tied that injury to oxidative mitochondrial DNA damage and showed that a mitochondria-targeted 8-oxoguanine DNA glycosylase-1 fusion (mOGG1), given after exposure, improves survival. This preprint is the 24-hour cell-state map. Mice breathed 500 ppm chlorine for 30 minutes, received 1 mg/kg mOGG1 at one hour, and gave their lungs to single-nucleus RNA sequencing.
Metal sites and redox
The lesion is 8-oxo-7,8-dihydroguanine on mtDNA, the guanine oxidation product next to a working respiratory chain. OGG1 is the glycosylase that starts base-excision repair of that base. Targeting it to mitochondria is the intervention. This paper does not name superoxide, hydrogen peroxide, peroxynitrite, or any Fe-S, heme, or copper site. Do not invent one. The redox actor is the 8-oxoG lesion and the enzyme that removes it.
What was measured
Air versus chlorine, with or without mOGG1. Four mice per group, both sexes. Thirty-nine integrated cell states. Four AT1/AT2 transitional phases (stress, proliferative, Krt8+ damage-associated, AT1-like). Pseudotime on alveolar and airway epithelium. Predicted IL-1 ligand-receptor traffic among neutrophils, macrophages, and epithelial states, including how mOGG1 redistributes those edges.
Caveats
One time point, modest n, transcriptome-only IL-1 claims, and biochemical 8-oxoG repair assumed from the prior mOGG1 study. This is a state atlas sitting on a mitochondrial DNA-repair drug, not a new metal-site mechanism.
What to do with it
When chlorine or other oxidant gases appear, route the story through mtDNA 8-oxoG and epithelial transitional states, not through a generic cytokine dump. mOGG1's signature here is a rearranged conversation, including Krt8+ and other DTAP cells, rather than immune silence.