Cardiac myosin contraction and mechanotransduction in health and disease

Cardiac myosin is the molecular motor that powers heart contraction by converting chemical energy from ATP hydro-lysis into mechanical force. The power output of the heart is tightly regulated to meet the physiological needs of the body. Recent multiscale studies spanning from molecules to tissues have revealed complex regulatory mechanisms that fine-tune cardiac contraction, in which myosin not only generates po-wer output but also plays an active role in its regulation. Thus, myosin is both shaped by and actively involved in shaping its mechanical environment. Moreover, these studies have shown that cardiac myosin-generated tension affects physiological processes beyond muscle contraction. Here, we review these novel regulatory mechanisms, as well as the roles that myosin-based force generation and mechanotransduction play in development and disease. We describe how key intra-and intermolecular interactions contribute to the regulation of myosin-based contractility and the role of mechanical forces in tuning myosin function. We also discuss the emergence of cardiac myosin as a drug target for diseases including heart failure, leading to the discovery of therapeutics that directly tune myosin contractility. Finally, we highlight some of the outstanding questions that must be addressed to better un-derstand myosin's functions and regulation, and we discuss prospects for translating these discoveries into precision medicine therapeutics targeting contractility and mechanotransduction.

Automated summary

Cardiac myosin, as a molecular motor, plays an important role in driving heart contraction and is involved in regulating the process. Studies have shown that tension generated by cardiac myosin affects physiological processes beyond muscle contraction. Furthermore, research on cardiac myosin as a target for heart disease treatment is ongoing.