Redox regulation of mitochondrial ATP synthase: implications for cardiac resynchronization therapy.

Molecular Medicine Redox Regulation of Mitochondrial ATP Synthase Implications for Cardiac Resynchronization Therapy

Cardiac resynchronization therapy and reverse molecular remodeling: importance of mitochondrial redox signaling.

Congestive heart failure is a devastating clinical syndrome characterized by progressive decline in cardiac performance with chamber dilation and multiple abnormalities of molecular signaling that adversely affect cell function and survival.1 Nearly 6 million Americans experience congestive heart failure, and more than 250,000 individuals die annually.2 Despite major advances in medical managem...

Modulation of mitochondrial proteome and improved mitochondrial function by biventricular pacing of dyssynchronous failing hearts.

BACKGROUND Cardiac resynchronization therapy (CRT) improves chamber mechanoenergetics and morbidity and mortality of patients manifesting heart failure with ventricular dyssynchrony; however, little is known about the molecular changes underlying CRT benefits. We hypothesized that mitochondria may play an important role because of their involvement in energy production. METHODS AND RESULTS Mi...

Regulation of mitochondrial ATP synthase in cardiac pathophysiology.

Mitochondrial function is paramount to energy homeostasis, metabolism, signaling, and apoptosis in cells. Mitochondrial complex V (ATP synthase), a molecular motor, is the ultimate ATP generator and a key determinant of mitochondrial function. ATP synthase catalyzes the final coupling step of oxidative phosphorylation to supply energy in the form of ATP. Alterations at this step will crucially ...

Mitochondrial Calpain-1 Disrupts ATP Synthase and Induces Superoxide Generation in Type 1 Diabetic Hearts: A Novel Mechanism Contributing to Diabetic Cardiomyopathy

Calpain plays a critical role in cardiomyopathic changes in type 1 diabetes (T1D). This study investigated how calpain regulates mitochondrial reactive oxygen species (ROS) generation in the development of diabetic cardiomyopathy. T1D was induced in transgenic mice overexpressing calpastatin, in mice with cardiomyocyte-specific capn4 deletion, or in their wild-type littermates by injection of s...