Getting to the Heart of Energy and Health

Many illnesses are increasingly being studied as metabolic diseases—cases where some aspect of the body’s capacity to produce energy has gone awry.

Shey-Shing Sheu, PhD, the William Wikoff Smith Professor of Cardiovascular Research, is part of a multidisciplinary team focused on mitochondria, the body’s cellular power plants. His team is bringing its insights to the study of cardiac disease, using advanced microscopy and other imaging techniques to peer into the dynamic processes of tiny mitochondria taking place within living cells.

When it comes to the heart, mitochondria have a Herculean task, as they keep the body’s most hardworking muscle pumping 24/7. Every day, the heart uses nearly 13 pounds of adenosine triphosphate (ATP) or 250 grams per hour. “Maybe most remarkably, it isn’t being produced at a steady quantity the entire time,” says Sheu. “The rate of ATP production changes rapidly with our level of physical activity, including fight or flight responses.”

His work seeks to understand the mechanism that underlies this variability, and how the heart modulates work rate and energy output to pump the blood perpetually and efficiently. This highly tuned process, called excitation-contraction bioenergetic coupling, refers to the initiation of electrical stimulus in the pacemaker cells and resulting contractile response of the heart muscles with sustainable energy—in other words, what makes the organ “pump”.

Sheu and his team have found that calcium ions seem to play a major role in coordinating ATP production and heart exertion. In each heartbeat, calcium ions are released from an intracellular store, flowing to various places within the cells. One of these areas, the mitochondrion, is where calcium ions appear to have a major say in the activity of ATP generation. In the event of increased exertion or sudden adrenaline surge, neurons that control the heart will fire more rapidly, which will release greater amounts of calcium ions and, in turn, signal mitochondria to produce more ATP.

“It’s beautiful how simple this association is,” Sheu says. “It allows the body to directly regulate the amount of energy it devotes to cardiac activity in proportion to the level of work required.”

Research shows that any disturbances in this energy cycle lead to human diseases including cardiac arrhythmias and heart failure. Therefore, the proteins that are involved in this calcium signaling process can serve as potential drug targets for treating these devastating diseases.