Disruption of cTnT-Mediated Sarcomere–Mitochondrial Communication Results in Dilated Cardiomyopathy
Our findings delineate a novel pathogenic mechanism underlying DCM, demonstrating that cTnT (p.K185E) sequence variation disrupts sarcomere-mitochondrial communication by weakening the interaction between cTnT and 14-3-3 proteins, thereby accelerating mitochondrial fragmentation through excessive activation of the 14-3-3 protein-mediated RAS/RAF1-p44/42-DRP1/MFF signaling axis. Therefore, therapeutic targeting of 14-3-3 proteins and p44/42 kinase activity may represent a promising strategy for DCM and other cardiac diseases associated with aberrant mitochondrial dynamics.
Authors
- Lingqun Ye (ORCID: https://orcid.org/0000-0002-8330-7483)
- Yuanhui Peng (ORCID: https://orcid.org/0009-0007-8137-1362)
- Huadong Li (ORCID: https://orcid.org/0000-0001-7085-9775)
- Jianyi Zhang (ORCID: https://orcid.org/0000-0002-3955-6554)
- Shijun Hu (ORCID: https://orcid.org/0000-0002-0068-8429)
- Kaili Hao
- Xinglong Han
- Ying Wang (ORCID: https://orcid.org/0000-0002-7852-386X)
- Yan Zhang (ORCID: https://orcid.org/0009-0008-5997-2724)
- Junwei Liu (ORCID: https://orcid.org/0000-0002-1320-4024)
- Miao Yu (ORCID: https://orcid.org/0000-0002-9104-4249)
- Zhen-Ao Zhao
- Zhenya Shen (ORCID: https://orcid.org/0000-0001-6503-6571)
- Hongchun Wu
- Baoqiang Ni
Institutions
- Hebei North University (CN)
- University of Alabama at Birmingham (US)
- Soochow University (CN)
- Wuhan Union Hospital (CN)
- Union Hospital (CN)
Publication Details
- Journal
- Circulation
- Published
- 2025-05-27
- DOI
- https://doi.org/10.1161/circulationaha.125.071523
- Citations
- 12
- Primary Topic
- Cardiomyopathy and Myosin Studies
- Type
- article
- Field-Weighted Citation Impact
- 16.66