Document Type

Article

Publication Date

1-9-2025

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).

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.

Creative Commons License

Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial 4.0 License

PubMed ID

39789731

Language

English

Share

COinS