Lysine succinylation-mediated energy metabolism imbalance drives brain injury in acute diquat poisoning.

Neurological damage induced by diquat (DQ) poisoning has garnered significant attention from researchers in recent years. This study represents the first systematic investigation into the molecular mechanisms underlying acute DQ-induced brain injury by integrating quantitative proteomics with lysine succinylation proteomics in male C57BL/6 J SPF mice exposed to 200 mg/kg DQ dibromide via a single oral gavage. The study revealed that DQ poisoning significantly downregulated lysine succinylation levels in mouse brain tissue, thereby inhibiting key mitochondrial energy metabolism pathways and disrupting glycine-serine-threonine metabolism and the one‑carbon folate pool pathway. These alterations led to energy metabolism disorders, exacerbated oxidative stress, and enhanced neuroinflammation, ultimately triggering neuronal apoptosis and neurological dysfunction. This study reveals the central regulatory role of abnormal lysine succinylation in DQ neurotoxicity, providing a novel potential target for clinical intervention.