CCDC141 is a Connectin/Titin and Nesprin-1 binding protein that adapts cardiomyocytes to mechanical stress.

ABSTRACT: The heart adapts to mechanical stresses such as hypertension, yet the underlying mechanisms remain poorly understood. We identify CCDC141 as a mechanoadaptive factor in cardiomyocytes. CCDC141 interacts with the sarcomeric connectin/titin filament system and the nuclear envelope protein nesprin-1, and localizes to the costameres in adult cardiomyocytes. CCDC141-KO mouse cardiomyocytes exhibit hypertrophy. Their mitochondria display abnormal alignment and fusion, are burdened by elevated ATP production, and show reduced spare respiratory capacity. Increased SERCA2a expression enhances Ca²⁺ handling within the sarcoplasmic reticulum of CCDC141-KO cardiomyocytes. During pressure overload-induced heart failure in mice, CCDC141 relocalizes to the nuclear envelope, suggesting a stress-responsive

SUBMITTER: Hanashima A 

PROVIDER: S-EPMC12657953 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature