<i>KLHL24</i> mutation drives intermediate filament degradation, mitochondrial dysfunction and fibrosis in heart failure patients
The deterioration of heart function in patients with KLHL24mut is driven by excessive proteasome-dependent degradation of multiple IF proteins across various cardiac cell types. Monotypic hiPSC-derived CMs and end-stage patient-derived cardiac explants from patients exhibit similar features, uncovering early pathological mechanisms and identifying a list of potential novel KLHL24mut target proteins. Finally, our findings validate that hiPSC-derived CMs represent a relevant model for future studies.
Authors
- Francis Palisson (ORCID: https://orcid.org/0000-0001-9196-841X)
- Roman I. Koning (ORCID: https://orcid.org/0000-0001-6736-7147)
- Rodrigo Ibañez‐Arenas
- Pilar Morandé
- Monique R.M. Jongbloed
- Peter A. van Veelen (ORCID: https://orcid.org/0000-0002-7898-9408)
- Veronika Ramovš (ORCID: https://orcid.org/0000-0001-7340-0724)
- Anupam Patra
- Aat A. Mulder (ORCID: https://orcid.org/0000-0002-4779-099X)
- Raffaella Dell’Oro (ORCID: https://orcid.org/0000-0002-9812-2879)
- Ignacia Fuentes (ORCID: https://orcid.org/0000-0002-8987-1317)
- Cristian Poblete (ORCID: https://orcid.org/0000-0003-0903-7400)
- María Joao Yubero
- C A Hübner
- H. Sophia Chen (ORCID: https://orcid.org/0000-0003-4355-2289)
- Andrés Schuster
- Rayman T.N. Tjokrodirijo (ORCID: https://orcid.org/0009-0007-4878-8385)
- J. Lauran Stöger (ORCID: https://orcid.org/0000-0002-4705-4837)
- Christine L. Mummery (ORCID: https://orcid.org/0000-0002-4549-6535)
- Karine Raymond (ORCID: https://orcid.org/0000-0001-5892-8117)
- Cristina Has (ORCID: https://orcid.org/0000-0001-6066-507X)
- Bernardo Morales Catalan
Institutions
- Universidad de Santiago de Chile (CL)
- Universidad Mayor (CL)
- Universidad del Desarrollo (CL)
- Inserm (FR)
- University of Freiburg (DE)
- Pontificia Universidad Católica de Chile (CL)
- Commissariat à l'Énergie Atomique et aux Énergies Alternatives (FR)
- Leiden University Medical Center (NL)
- Novo Nordisk Foundation (DK)
- University Medical Center Freiburg (DE)
- CEA Grenoble (FR)
- Clínica Las Condes (CL)
- Universidad Bernardo O'Higgins (CL)
- Netherlands Metabolomics Centre (NL)
- Université Grenoble Alpes (FR)
Publication Details
- Journal
- Cardiovascular Research
- Published
- 2025-11-11
- DOI
- https://doi.org/10.1093/cvr/cvaf231
- Primary Topic
- Mitochondrial Function and Pathology
- Type
- article
- Field-Weighted Citation Impact
- 0.00