Impairment of the ER/mitochondria compartment in human cardiomyocytes with PLN p.Arg14del mutation.

ABSTRACT: The phospholamban (PLN) p.Arg14del mutation causes dilated cardiomyopathy, with the molecular disease mechanisms incompletely understood. Patient dermal fibroblasts were reprogrammed to hiPSC, isogenic controls were established by CRISPR/Cas9, and cardiomyocytes were differentiated. Mutant cardiomyocytes revealed significantly prolonged Ca²⁺ transient decay time, Ca²⁺ -load dependent irregular beating pattern, and lower force. Proteomic analysis revealed less endoplasmic reticulum (ER) and ribosomal and mitochondrial proteins. Electron microscopy showed dilation of the ER and large lipid droplets in close association with mitochondria. Follow-up experiments confirmed impairment of the ER/mitochondria compartment. PLN p.Arg14del end-stage heart failure samples revealed

SUBMITTER: Cuello F 

PROVIDER: S-EPMC8185541 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature