Key result
Targeting cardiac ubiquitination offers therapeutic promise in diabetic cardiomyopathy via protein and mitochondrial regulation.
Why the study?
Ubiquitination links diabetic stress to changes in protein turnover, signaling-complex assembly, and organellar quality control in diabetic cardiomyopathy, but direct evidence must be distinguished from other disease models alongside limitations in therapeutic selectivity, safety, and human validation.
This review details how E3 ubiquitin ligases and deubiquitinating enzymes regulate metabolic dysfunction, mitochondrial quality control, inflammation, and fibrosis across distinct cardiac cell types in diabetic cardiomyopathy, highlighting the need for substrate-resolved and cell-specific studies to guide safe therapeutic targeting.
Ubiquitination pathways in DCM merit targeted study across cell types; leaves open whether specific ligase modulation improves clinical outcomes.
Diabetic cardiomyopathy (DCM) involves metabolic dysfunction and adverse myocardial remodeling that can progress to heart failure. Ubiquitination links diabetic stress to changes in protein turnover, signaling-complex assembly, and organellar quality control. This review examines these mechanisms across cardiomyocytes, cardiac fibroblasts, endothelial cells, and immune cells, distinguishing direct DCM evidence from findings in other disease models. We compare E3 ubiquitin ligases and deubiquitinating enzymes that converge on lipid metabolism, mitochondrial function, inflammation, and regulated cell death. Their effects depend on substrate identity, ubiquitin-chain topology, cellular context, and interactions with other post-translational modifications. We also assess pharmacological modulation, cardiac-directed gene delivery, and targeted protein degradation, while identifying limitations in selectivity, safety, and human validation. Substrate-resolved and cell-specific studies are needed to determine which ubiquitination pathways can be targeted without disrupting essential cardiac proteostasis.
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Jiang et al. (2026) conducted a review in Diabetic cardiomyopathy. Ubiquitination regulates protein turnover, mitochondrial function, and inflammation in diabetic cardiomyopathy, requiring substrate-resolved and cell-specific validation for therapeutic targeting.
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