For the heart to function properly, there needs to be a contractile capacity and a constant and controlled energy production so that all the tissues receive the necessary oxygen. The mitochondrion is the subcellular organelle responsible for coordinating both processes (energy production and calcium control as a regulator of muscle contraction) and is also the largest cellular producer of reactive oxygen species (ROS), which at high levels is toxic to humans. cell.

In addition, the researchers explain, in order to ensure adequate function of the heart muscle cells, the mitochondria must maintain a correct internal structure and be able to control the excessive production of ROS caused by contractile over-exertion in situations of overwork, hypertension or other types of stress.

In the research coordinated by José Antonio Enríquez, three independent models of heart failure have been evaluated that present with different symptoms: chronic tachycardia, chronic hypertension and myocardial ischemia with hypertrophy.

Regardless of the type of stress, cardiac damage is induced in all three models. Our results indicate that, says Rebeca Acín Pérez, first author of the work, “regardless of the initial cause that causes heart failure, the three models share common characteristics and involve the mitochondria.” Thus, explains the researcher, in the three models that have been studied, an increase in mitochondrial ROS production was induced, followed by changes in the mitochondrial inner membrane morphology and loss of capacity to produce energy by the mitochondria that lead at the death of cardiomyocytes.

The elimination of the OMA1 protease prevents heart failure in the three models studied and, therefore, plays a direct role in the protection of cardiomyocytes
The researchers also saw that activation of the OMA1 protease is necessary for the morphological alterations of the mitochondrial inner membrane to be triggered. This protease, explains Acín Pérez, “processes its only target described to date (OPA1), a mitochondrial protein responsible for maintaining the characteristic structure in mitochondria ridges.”

In the study, it has been seen that in the mouse model the elimination of the OMA1 protease prevents heart failure in the three models studied and, therefore, plays a direct role in the protection of cardiomyocytes. These results, the researchers conclude, identify OMA1 as a promising therapeutic target for heart failure.