DWORF Gene Therapy Improves Cardiac Calcium Handling and Mitochondrial Function.

ABSTRACT:

Background

Calcium (Ca²⁺) dysregulation is a hallmark of heart failure, impairing excitation-contraction coupling and contributing to pathological remodeling. The sarco/endoplasmic reticulum Ca²⁺ ATPase isoform 2a (SERCA2a) mediates Ca²⁺ reuptake into the sarcoplasmic reticulum (SR) during diastole, but its activity declines in failing hearts. DWORF (dwarf open reading frame), a newly identified cardiac microprotein, enhances SERCA2a activity and improves cardiomyocyte Ca²⁺ cycling and contractility. SR Ca²⁺ release also influences mitochondrial metabolism and ATP production. Here, we investigated whether DWORF overexpression improves SR Ca²⁺ handling, augments mitochondrial Ca²⁺ signaling, and protects ag

SUBMITTER: Brito-Estrada O 

PROVIDER: S-EPMC12676482 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature