The failing heart undergoes structural cardiac remodeling, impaired excitation–contraction (EC) coupling, and metabolic substrate utilization, which consequently induces energetic deficit and oxidative stress. Mitochondria play a central role in many of these processes because they are the main source of cellular ATP, in addition to reactive oxygen species (ROS). Mitochondrial function is critically controlled by calcium. Thus, calcium homeostasis within the myocardium is essential both for contraction but also to modulate ATP production to ensure the homeostasis of energy demand and supply. Disruption of the t-tubules, and mitochondrial uptake of calcium, may play a causative role in driving impaired mitochondrial function and energy metabolism in heart failure. Recent evidence has indicated that the assembly of mitochondrial supercomplexes are important for maintaining efficient respiration and lowering ROS production in the mitochondria and their assembly may be disrupted in heart failure. However whether this is related to energetic deficit in the heart remains to be fully understood.
Collaborators include: Åsa Birna Birgisdottir (UiT), Yakubu Princely Abudu (UiT)