The heart imports lactate straight into its mitochondria to keep beating under stress — in mice and human heart cells

Edited by Samael A. Tejada, Founder & Editor-in-Chief

Lactate has spent a century being mislabeled as a waste product. This study gives it a precise address and a precise job: a fuel delivered directly inside the heart's mitochondria through a named transporter, in a compartment separate from glucose burning, so both can run at once. That is a mechanism paper of the first rank — and, as the authors themselves frame it, a target for future heart-failure research, not a treatment anyone can use today.

What exactly did the Utah team find?

Carbohydrate oxidation was thought to converge on one doorway: pyruvate made in the cytosol, carried into mitochondria by the mitochondrial pyruvate carrier (MPC). Cluntun and colleagues found that in mouse myocardium, glucose-derived carbon was still oxidized when the MPC was genetically absent. The explanation was a second doorway. MCT1 — a transporter previously known from the cell's outer membrane — also resides in the inner mitochondrial membrane of mouse and human cardiomyocytes, where it imports lactate into the organelle. Inside, mitochondrial LDHB oxidizes that lactate to pyruvate and NADH, feeding the tricarboxylic acid cycle and sustaining ATP production.

Why does burning glucose and lactate in separate compartments matter?

The spatial separation is the trick. Because glucose is burned in the cytosol while lactate is burned inside mitochondria, the two energy-generating reactions can proceed simultaneously instead of competing for the same doorway. The team describes this as a parallel lactate-based pathway for carbohydrate oxidation that can sustain cardiac energetics and maintain heart structure and function under diverse stress conditions — neurohormonal, hemodynamic and ischemic stress among them. Genetic ablation of MCT1 abolished mitochondrial lactate oxidation, disrupted that adaptation, and accelerated the development of heart failure with higher mortality in the model.

What could this mean for heart failure — and what are the limits?

The therapeutic idea writes itself: if a stressed or injured heart depends on mitochondrial lactate import, then enhancing that pathway might help hearts recover after heart attack or in heart failure — co-senior author Stavros Drakos frames the long-term goal as helping heart muscle heal by using lactate better. The limits are equally clear. The functional experiments are in mice; the human contribution is the demonstration that MCT1 sits in the inner mitochondrial membrane of human heart cells, not a human treatment result. No drug targeting this pathway has been tested in a person, and lactate metabolism is systemic — any future therapy would need to move the heart's pathway without disturbing lactate handling everywhere else.

Where the evidence stands

• Established: The heart oxidizes multiple fuels including glucose and lactate; lactate is a circulating energy substrate, not merely a waste product; and the mitochondrial pyruvate carrier was the canonical route for carbohydrate carbon into mitochondria.
• Preliminary: In mouse myocardium and human cardiomyocyte samples (Nature, Oct 28, 2026; DOI 10.1038/s41586-026-11182-3), MCT1 in the inner mitochondrial membrane imported lactate for oxidation by LDHB, sustaining cardiac energetics without the pyruvate carrier; MCT1 ablation abolished that oxidation and accelerated stress-induced heart failure in mice.
• Absent: Any human treatment, drug or intervention targeting mitochondrial lactate import, and any clinical outcome data in heart-failure or heart-attack patients.