biorxiv2026-10-21score 84
Mitochondria-targeted OGG1 remaps alveolar transitional states after chlorine injures mtDNA
Dubey, Crossman and Matalon follow chlorine inhalation with a mitochondria-targeted 8-oxoguanine DNA glycosylase-1 fusion (mOGG1) and, at 24 hours, single-nucleus RNA sequencing of mouse lung. They previously showed that oxidative mitochondrial DNA damage drives chlorine lung injury and that post-exposure mOGG1 improves survival. This preprint asks which epithelial and immune states carry that effect. Chlorine expands heterogeneous alveolar transitional programs, including a Krt8+ damage-associated state, and complicates interleukin-1 ligand-receptor traffic among neutrophils, macrophages, and epithelium. mOGG1 does not globally silence that network. It redistributes who talks to whom, including selected transitional populations. The named chemistry is 8-oxoguanine on mtDNA, the base-excision lesion of oxidative guanine. No Fe-S nuclearity is claimed.
