LARP7, a new ROS sensor, protects against heart failure by enhancing mitochondrial biogenesis

LARP7 controls the SIRT1 activity and homeostasis, which is essential for mitochondrial biogenesis, energy production and cardiac function. The deprivation of LARP7 resulted from the activation ATM pathway attenuates the mitochondrial function and biogenesis and leads to the cardiomyopathy and heart failure. Method: Heart morphology and functions were assessed by gross anatomy, serial echocardiography and histology on sections; Mitochondrial morphology and activity were evaluated by TEM and seahorse assays. The therapeutic potential of LARP7 in heart failure was evaluated in mouse myocardial infarction model either with AAV9 infection or pharmacological inhibitor. We used RNA-seq to profile and compare the transcriptome in the hearts of wildtype and LARP7 conventional knockout mouse (LARP7-/-) and conditional knockout mouse (LARP7 LoxP).