Lack of RNF10 in heart muscle cells weakens mitochondrial cleanup and leads to harmful heart enlargement

Cardiac-specific RNF10 knockout (RNF10-CKO) mice developed cardiac hypertrophy with aging, characterized by exacerbated myocardial fibrosis and impaired cardiac function.

• Multiple chronic stressors, including aging and obesity, induced cardiac RNF10 expression.
• Aged RNF10-CKO mice exhibited elevated levels of reactive oxygen species (ROS) and reduced mitochondrial membrane potential.
• Transmission electron microscopy revealed mitochondrial abnormalities such as rounding and cristae disorganization in RNF10-CKO mice.
• Ang II exposure in RNF10-CKO mice resulted in cardiomyocyte hypertrophy and cardiac dysfunction similar to that observed in aged RNF10-CKO mice.
• Chronic stressors increased RNF10 expression, which mediated the polyubiquitination of the mitochondrial protein mitofusin 2 (MFN2).
• RNF10-mediated mitophagy is dependent on MFN2 and involves the recruitment of Parkin and the autophagy adaptor sequestosome 1 (SQSTM1/p62).

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