Mitochondria as central regulators of cardiac adaptation to stress and aging
Mitochondria as central regulators of cardiac adaptation to stress and aging
The heart is a highly adaptable organ that changes its structure and function to meet the body’s demands, a process known as cardiac remodelling. Its incessant beating requires an enormous amount of energy, supplied by mitochondria, the power plants of the heart muscle cell. The success of cardiac remodelling depends on how well mitochondria can adapt. Yet the mechanisms behind this adaptation, in health and disease, remain poorly understood, even though this knowledge is essential to preserve or improve heart function.
In his thesis Pablo Sánchez Aguilera describes the role of mitochondria in chronic disease, explaining their normal functions and how these change during disease. Additionally, he used cultured heart muscle cells to compare two faces of remodelling: the growth signal IGF-1, which rises during exercise and boosts mitochondrial energy production, and the stress protein ATPIF-1, which rises in failing hearts and pushes mitochondria toward dysfunction. Finally, he studied ATPIF-1 in two animal models: the sudden remodelling induced by temporary blood flow interruption, and the gradual remodelling of aging.
The findings show that mitochondria respond in opposite ways to sudden and gradual stress, and that the same protein can be harmful in one setting and indispensable in another. Removing ATPIF-1 improved how mitochondria handle calcium and modestly improved young heart function yet did not protect against temporary ischemia. In old hearts it blocked the clearance of damaged mitochondria, leading to scarring and loss of function in both ventricles. ATPIF-1 is therefore not the treatment target it appeared to be.