Unveiling Novel Biomarkers: Ferroptosis and m1A in the Progression of Nanographene‐Induced Lung Fibrosis

Graphene, a novel 2D carbon-based material, has become integral to energy capture and storage facilities in wind and photovoltaic energy. Its widespread application has escalated concerns regarding occupational inhalation exposure, necessitating urgent identification of associated health risks and preventive strategies. Divergent outcomes are reported regarding nanographene-induced pulmonary fibrosis. Intriguingly, multiple modes of programmed cell death, including ferroptosis, are discovered to have essential regulatory roles in the pathological process. Nevertheless, their relationship with graphene exposure and the resulting toxic effects remains unexplored. In this study, it is demonstrated that escalating graphene exposure durations and doses induced tissue-specific organ damage, predominantly localized to the pulmonary and immune systems. Notably, cellular ferroptosis is accompanied by lung tissue fibrosis, a finding further confirmed by metabolomics. Furthermore, 1-methyladenosine is identified as a responsive biomarker of graphene exposure, with functional validation implicating tRNA methyltransferase 6 (TRMT6 and tRNA methyltransferase 61A (TRMT61A). Collectively, the findings suggest that m1A mediates critical signaling during the progression of fibrosis and ferroptosis induced by graphene exposure and can serve as a potential biomarker of graphene exposure. Targeting TRMT6/TRMT61A may offer therapeutic avenues against graphene-induced toxicity.