Myosin light-chain 4 gene-transfer attenuates atrial fibrosis while correcting autophagic flux dysregulation.

ABSTRACT:

Objectives

To determine the role of MYL4 regulation of lysosomal function and its disturbance in fibrotic atrial cardiomyopathy.

Background

We have previously demonstrated that the atrial-specific essential light chain protein MYL4 is required for atrial contractile, electrical, and structural integrity. MYL4 mutation/dysfunction leads to atrial fibrosis, standstill, and dysrhythmia. However, the underlying pathogenic mechanisms remain unclear.

Methods and results

Rats subjected to knock-in of a pathogenic MYL4 mutant (p.E11K) developed fibrotic atrial cardiomyopathy. Proteome analysis and single-cell RNA sequencing indicate enrichment of autophagy pathways in mutant-MYL4 atrial dysfunction. Immunofluorescence and electron microscopy revealed undegraded autophagic ves

SUBMITTER: Zhong Y 

PROVIDER: S-EPMC9860351 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature