Heart failure & cardiomyopathies
Jmjd4 Facilitates Pkm2 Degradation in Cardiomyocytes and Is Protective Against Dilated Cardiomyopathy
An erratum to this article was published (Circulation, 9 Jul 2024 ↗)
Authors' conclusion
Our results identified a novel role of Jmjd4 in maintaining metabolic homeostasis in adult cardiomyocytes by degrading Pkm2
Study context
- Population
- Patients with dilated cardiomyopathy (DCM) (Jmjd4 expression) and mice with cardiomyocyte-specific Jmjd4 deletion or overexpression
Main finding
As reported in the abstract
- Jmjd4 expression significantly decreased in hearts of patients with DCM
- Induced cardiomyocyte-specific Jmjd4 deletion led to spontaneous DCM with severely impaired mitochondrial respiration
- Pkm2 drastically accumulated in hearts with Jmjd4 deleted
- Jmjd4 interacts with Hsp70 to mediate Pkm2 degradation via chaperone-mediated autophagy, dependent on Jmjd4 hydroxylation of Pkm2 K66
- TEPP-46 (Pkm2 agonist) showed significant therapeutic effect on DCM induced by Jmjd4 deficiency and on HF induced by pressure overload
Original publication
Jmjd4 Facilitates Pkm2 Degradation in Cardiomyocytes and Is Protective Against Dilated Cardiomyopathy. Circulation. Published 17 April 2023. doi:10.
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