Researchers at the University of Utah have discovered that heart muscle cells burn glucose in the cell cytosol while simultaneously using lactate inside their mitochondria, relying on a molecule called MCT1 to transport lactate into the inner mitochondrial membrane to keep the organelle fueled during severe stress.
Maintaining an uninterrupted energy supply is one of the most demanding physical challenges the human body faces. The heart beats constantly regardless of the body’s overall energy reserves, shifting between different fuel sources to match metabolic needs. While most tissues struggle to process glucose and lactate at the same time—with one fuel typically suppressing the utilization of the other—cardiac tissue manages a unique metabolic trick.
Laboratory work and experiments with animal models detailed in research published in Nature have revealed how cardiac muscle cells pull off this dual-fuel capability. Scientists identified that the separation between glucose and lactate metabolism relies on a specific transporter molecule that moves lactate past the outer boundaries of the cell and directly into the power-generating structures inside.
MCT1 Resides in the Inner Mitochondrial Membrane
The transport mechanism depends on monocarboxylate transporter 1, commonly known as MCT1.
We further observe that MCT1, traditionally localized to the plasma membrane, also resides in the inner mitochondrial membrane of mouse and human cardiomyocytes.
Study authors, Nature
To uncover how this system operates under pressure, researchers generated adult cardiac-specific knockout models. When investigators genetically ablated MCT1 in these experimental models, the consequences for the heart were severe. Blocking mitochondrial lactate import disrupted the organ’s energy balance and stripped away its ability to adapt to hemodynamic, neurohormonal, or ischemic stress.
Genetic ablation of MCT1 abolishes mitochondrial lactate oxidation, disrupts adaptation to neurohormonal, hemodynamic or ischemic stress and accelerates the development of heart failure with enhanced mortality.
Study authors, Nature
Cardiovascular Disease and the Search for Heart Muscle Repair
Cardiovascular conditions such as heart failure frequently disrupt the complex energy flow required to keep cardiac tissue functioning. When the heart experiences severe stress, having a parallel lactate-based oxidation pathway acts as a crucial safety valve for cellular energetics, helping maintain myocardial structure and function under diverse physiological challenges.
This appears to be a critical backup system for heart function.
Gregory Ducker, PhD, assistant professor of biochemistry at University of Utah Health
Ducker emphasized the operational importance of this metabolic pathway during high-stress scenarios. In an emergency, we would really, really rely on this,
he noted.
The discovery uncovers a previously unrecognized requirement for lactate to fuel injured heart tissue. Rather than viewing lactate as a simple metabolic waste product released into the bloodstream, researchers suggest that medical strategies could eventually learn to enhance the heart’s ability to consume it as a valuable energy source.
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.
Stavros Drakos, MD, PhD, Professor of Medicine at University of Utah Health
By optimizing this energy pathway, clinicians might one day improve myocardial function in patients recovering from heart attacks or living with chronic heart failure. As investigators continue to map these cellular mechanisms, the long-term objective remains centered on finding ways to target the heart muscle so it can better repair itself.
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.
Gregory Ducker, PhD, assistant professor of biochemistry at University of Utah Health