The phospholamban R14del generates pathogenic aggregates by impairing autophagosome-lysosome fusion.

ABSTRACT: Phospholamban (PLN) plays a crucial role in regulating sarcoplasmic reticulum (SR) Ca²⁺ cycling and cardiac contractility. Mutations within the PLN gene have been detected in patients with cardiomyopathy, with the heterozygous variant c.40_42delAGA (p.R14del) of PLN being the most prevalent. Investigations into the mechanisms underlying the pathology of PLN-R14del have revealed that cardiac cells from affected patients exhibit pathological aggregates containing PLN. Herein, we performed comprehensive molecular and cellular analyses to delineate the molecular aberrations associated with the formation of these aggregates. We determined that PLN aggregates contain autophagic proteins, indicating inefficient degradation via the autophagy pathway. Our findings demonstrate that the ex

SUBMITTER: Vafiadaki E 

PROVIDER: S-EPMC11554986 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature