Document Type
Article
Publication Date
1-9-2025
Abstract
Over the past 25 years, nuclear envelope (NE) perturbations have been reported in various experimental models with mutations in the LMNA gene. Although the hypothesis that NE perturbations from LMNA mutations are a fundamental feature of striated muscle damage has garnered wide acceptance, the molecular sequalae provoked by the NE damage and how they underlie disease pathogenesis such as cardiomyopathy (LMNA cardiomyopathy) remain poorly understood. We recently shed light on one such consequence, by employing a cardiomyocyte-specific Lmna deletion in vivo in the adult heart. We observed extensive NE perturbations prior to cardiac function deterioration with collateral damage in the perinuclear space. The Golgi is particularly affected, leading to cytoprotective stress responses that are likely disrupted by the progressive deterioration of the Golgi itself. In this review, we discuss the etiology of LMNA cardiomyopathy with perinuclear ‘organelle trauma’ as the nexus between NE damage and disease pathogenesis.
Recommended Citation
Choi, Jason C., "Perinuclear Organelle Trauma at the Nexus of Cardiomyopathy Pathogenesis Arising From Loss of Function LMNA Mutation" (2025). Center for Translational Medicine Faculty Papers. Paper 127.
https://jdc.jefferson.edu/transmedfp/127
Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial 4.0 License
PubMed ID
39789731
Language
English
Comments
This article is the author's final published version in Nucleus, Volume 16, Issue 1, January 2025, Article number 2249500.
The published version is available at https://doi.org/10.1080/19491034.2024.2449500.
Copyright © 2025 The Author(s).