Adeno-associated virus-mediated gene delivery of <i>Perm1</i> enhances cardiac contractility in mice

Reduced muscle contractility and mitochondrial bioenergetics are the hallmarks of systolic heart failure. There is currently no therapy targeting both. Here, we show that gene delivery of <i>Perm1</i> via adeno-associated virus (AAV) simultaneously enhances cardiac contractility and mitochondrial biogenesis in C57BL6 mice. Moreover, we found that PERM1 interacts with troponin C (TnC), a key contractile protein in striated muscle, and that AAV-<i>Perm1</i> led to the upregulation of TnC. This study suggests that gene delivery of <i>Perm1</i> may be a novel therapeutic approach to treat systolic heart failure by simultaneously restoring cardiac contractility and mitochondrial bioenergetics.<b>NEW & NOTEWORTHY</b> <i>Perm1</i> gene delivered with AAV9 enhances cardiac contractility in mice, and it is concomitant with the increase of mitochondrial bioenergetics and upregulation of TnC. This is the first study showing that PERM1, previously known as a striated muscle-specific mitochondrial regulator, also positively regulates cardiac contractility.