Dusp15 modulates mtHsp70 Thr116 phosphorylation state to preserve mito-UPR and attenuate cardiac dysfunction in diabetic cardiomyopathy - PubMed
5 days ago
- #Mitochondrial proteostasis
- #Dusp15-mtHsp70 axis
- #Diabetic cardiomyopathy
- Dusp15 modulates mtHsp70 Thr116 phosphorylation to protect against diabetic cardiomyopathy (DCM).
- Dusp15 levels are reduced in diabetic hearts, correlating with impaired cardiac function.
- Cardiomyocyte-specific Dusp15 knockout worsens diabetic injury, while Dusp15 gain-of-function improves cardiac outcomes.
- Dusp15 interacts with mtHsp70, supporting mitochondrial proteostasis and the mitochondrial unfolded protein response (mito-UPR).
- mtHsp70T116A knock-in mice show protection against diabetic cardiac dysfunction.
- Dapagliflozin (DAPA) benefits diabetic hearts, with reduced efficacy in Dusp15 knockout mice.
- Targeting the Dusp15-mtHsp70 axis may offer therapeutic potential for DCM.