Reposted from U of U Health.
The heart is the hardest-working muscle in the body, beating constantly no matter what the body's energy reserves look like. Maintaining energy flow to the heart is a complex process that can break down during common but severe cardiovascular disease conditions, such as heart failure. Researchers previously knew that heart muscle appears to use an unusual metabolic strategy to always get enough energy: using two carbohydrate energy sources, glucose and lactate, at the same time. In most human tissues, using more glucose makes it harder to use lactate, and vice versa, but the heart is different.
Now, researchers have found a unique cell-level difference that helps keep heart muscle fueled up: the ability to burn glucose in the cytosol (the main body of the cell) while burning lactate in the mitochondria (the powerhouse of the cell). This spatial separation allows both energy-generating reactions to happen simultaneously, helping keep the heart fueled up no matter the energy source. While mostly dispensable to daily life, this process is crucial to preventing heart failure when the heart is stressed.
The results are published in Nature.
"This appears to be a critical backup system for heart function," said Gregory Ducker, assistant professor of biochemistry at University of Utah Health and senior author on the paper. "In an emergency, we would really, really rely on this."
The researchers found that the separation between glucose and lactate metabolism depends on a molecule called MCT1, which moves lactate to the mitochondrial interior. Genetic mutations in MCT1 prevent lactate from entering the mitochondria and disrupt the heart's energy balance, leading to heart failure when stressed. These results uncover a new requirement for lactate to fuel the injured heart and point to new therapeutic targets to re-energize the heart during heart failure.
"Our findings help point to new areas in which we could target the heart muscle to benefit and repair itself by allowing it to use lactate better," Ducker said. "That's the long-term goal: to help the heart muscle heal."
The discovery of a new pathway through which the heart muscle can use lactate to generate energy opens promising opportunities for developing new treatments for serious heart conditions, including heart failure and heart attacks.
"Rather than simply releasing lactate into the bloodstream as a waste product, we may be able to enhance the heart's ability to use it as a valuable source of energy," said co-senior author Stavros Drakos, professor of medicine at U of U Health. "By optimizing this process, we could potentially improve heart muscle function in patients suffering from heart failure or heart attacks."
These results are published in Nature as "MCT1-dependent mitochondrial lactate import sustains cardiac metabolism."
This work was funded by the National Institutes of Health, including the National Heart, Lung, and Blood Institute, the National Institute of Diabetes and Digestive and Kidney Diseases, the National Cancer Institute and the National Institute of General Medical Sciences; the U.S. Department of Veterans Affairs; the American Heart Association; and the Burroughs Wellcome Fund. Content is solely the responsibility of the authors and does not necessarily represent the official views of the funders.
