ALDOB K87 lactylation drives mitochondrial fission and metabolic reprogramming in pulmonary hypertension - PubMed
7 hours ago
- #ALDOB lactylation
- #pulmonary hypertension
- #mitochondrial fission
- ALDOB-K87 lactylation drives mitochondrial fission and metabolic reprogramming in pulmonary hypertension (PH).
- Hypoxia induces ALDOB-K87 lactylation in PASMCs, amplifying glycolysis and lactate accumulation in a self-reinforcing loop.
- ALDOB lactylation recruits DRP1 to mitochondria via SENP3-mediated deSUMOylation, leading to mitochondrial fragmentation and worsening PASMC proliferation and migration.
- Sirtuin 1 acts as a delactylase for ALDOB; its downregulation in PH sustains lactylation-driven pathology.
- Genetic or pharmacological inhibition of ALDOB lactylation reduces mitochondrial fission and PH progression, highlighting a lactate-ALDOB-DRP1 axis as a therapeutic target.