TrxR2 Lactylation Facilitates Mitochondrial Protection and Endothelial Ferroptosis Resistance in Diabetic Cardiomyopathy - PubMed
5 days ago
- #TrxR2
- #Diabetic Cardiomyopathy
- #Ferroptosis
- TrxR2 lactylation plays a critical role in mitochondrial protection and endothelial ferroptosis resistance in diabetic cardiomyopathy (DCM).
- Endothelial TrxR2 deficiency worsens cardiac microvascular dysfunction and accelerates DCM progression.
- TrxR2 overexpression and Kukoamine B treatment inhibit mitochondria-associated ferroptosis by promoting SCP2 degradation and blocking ACSL4 mitochondrial translocation via mitophagy.
- TrxR2 maintains TUFM expression by scavenging oxygen radicals, facilitating AMPK mitochondrial translocation for mitophagy activation.
- TrxR2 undergoes lactylation at lysine 340, mediated by AARS2 and lactate accumulation in diabetic hearts, enhancing mitoTrxR activity and ferroptosis resistance.
- The study suggests TrxR2 lactylation as a promising therapeutic target for managing diabetic complications.