STING-driven mitochondrial metabolism reverses cisplatin resistance via MDH2 desuccinylation in non-small cell lung cancer - PubMed
5 hours ago
- #cisplatin-resistance
- #NSCLC
- #mitochondrial-metabolism
- STING-driven mitochondrial metabolism reverses cisplatin resistance in non-small cell lung cancer (NSCLC).
- Key protein STING regulates cisplatin resistance via proteomics and in vitro/in vivo validation.
- Succinylation post-translation modifications (PTMs) of MDH2 linked to STING-mediated resistance reversal.
- STING stabilizes mitochondrial desuccinylase SIRT5, reducing TRIM21-SIRT5 interaction.
- SIRT5 promotes desuccinylation of MDH2 at lysine 314, impairing its enzymatic function.
- MDH2 desuccinylation leads to mitochondrial respiratory dysfunction and mtDNA damage.
- Activation of cGAS-STING signaling pathway restores cisplatin sensitivity in resistant NSCLC cells.
- STING/MDH2 desuccinylation feedback loop integrates metabolic reprogramming with immune activation.
- STING and Succ-MDH2 (Lys 314) identified as potential therapeutic targets for cisplatin-resistant NSCLC.