YAP and WWTR1/TAZ Connect Mechanotransduction and Mitochondrial Metabolism in Cardiac Hypertrophy and Ventricular Remodeling.

Cardiac hypertrophy is a mechanometabolic remodeling process shaped by mechanical load, matrix stiffness and mitochondrial adaptation. YAP and TAZ, encoded by YAP1 and WWTR1, are paralogous, non-DNA-binding transcriptional co-activators that link cytoskeletal tension to TEAD-dependent transcription. This review organizes current evidence along a mechanical stress-YAP/TAZ activation-mitochondrial remodeling-ventricular remodeling axis and distinguishes direct human myocardial data, animal cardiac mechanisms, related cardiovascular or in vitro evidence, and cross-disease extrapolation. Experimental studies suggest that TEAD1 supports mitochondrial gene programs, transient YAP activation promotes glycolytic compensation during early pressure overload, whereas sustained Yap1 activation may impair mitochondrial biogenesis. Cell-specific studies further implicate fibroblast, endothelial, immune and epicardial programs, although many data derive from non-hypertrophic contexts. Thus, the adaptive-to-maladaptive YAP/TAZ model remains provisional. Human lineage-resolved data are limited, and no YAP/TAZ-targeted therapy is established for cardiac hypertrophy.