Cytosolic Glucose and Mitochondrial Lactate Oxidation Prevent Energetic Collapse

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 like heart failure.

Researchers previously knew that heart muscle seems to do an unusual metabolic trick 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.

This appears to be a critical backup system for heart function. In an emergency, we would really, really rely on this.”

Gregory Ducker, PhD, Study Senior Author and Assistant Professor, Biochemistry, University of Utah Health

The researchers found that the separation between glucose and lactate metabolism depends on a molecule called MCT1, which moves lactate to the inside of the mitochondria. 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 suggest 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. That’s the long-term goal: to help the heart muscle heal.” Gregory Ducker, PhD

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,” says Stavros Drakos, MD, PhD, professor of medicine at University of Utah Health and co-senior author of the study. “By optimizing this process, we could potentially improve heart muscle function in patients suffering from heart failure or heart attacks.”