University of Utah Health researchers discovered a novel backup energy system in the heart that utilizes lactate alongside glucose. Published in Nature in October 2026, the study reveals that cardiomyocytes spatially separate metabolism by burning glucose in the cytosol and lactate in mitochondria via the MCT1 transporter. This dual pathway prevents energy failure when the heart is stressed, opening prospective therapeutic targets for heart failure and myocardial infarction.
MCT1 role and disruption in heart failure
- ▪Genetic disruption or loss of monocarboxylate transporter 1 impairs cardiac energy balance, accelerating heart failure, ventricular hypertrophy, and mortality under stress.
- ▪University of Utah Health researchers Gregory Ducker and Stavros Drakos identified mitochondrial lactate utilization pathways as novel therapeutic targets for heart failure and heart attacks.
- ▪Mitochondrial lactate oxidation functions as a critical cardiac backup energy system that is dispensable during routine activity but essential under physiological stress.
Mechanism of cardiac mitochondrial lactate oxidation
- ▪Administering the monocarboxylate transporter 1 inhibitor AZD3965 to MPC1-deficient mice ablated glucose carbon contribution to cardiac TCA cycle metabolites.
- ▪In experiments on MPC1-knockout mice, University of Utah researchers observed sustained carbohydrate oxidation in heart muscle despite mitochondrial pyruvate carrier deficiency.
- ▪University of Utah researchers discovered that the monocarboxylate transporter 1 molecule is localized on the inner mitochondrial membrane of cardiomyocytes.
- ▪Conventional metabolic models posited that lactate oxidation requires cytosolic conversion to pyruvate before mitochondrial entry via the mitochondrial pyruvate carrier.
Simultaneous substrate utilization in heart muscle
- ▪Cardiomyocytes achieve simultaneous energy generation by burning glucose in the cytosol while burning lactate within the mitochondria.
- ▪Unlike most human tissues where elevated glucose consumption restricts lactate utilization due to cytosolic NAD+ competition, heart muscle oxidizes both substrates simultaneously.
Cellular energy and fuel sources
- ▪In mammalian physiology, circulating lactate turnover exceeds that of glucose, establishing lactate production as the dominant mode of cytosolic NAD+ regeneration.
- ▪Mitochondrial oxidation of carbon fuels accounts for more than 95% of total human ATP energy production.
Study funding and support
- ▪The cardiac metabolism study published in Nature was funded by the National Institutes of Health, U.S. Department of Veterans Affairs, and American Heart Association.
- ▪The Burroughs Wellcome Fund also provided funding support for the University of Utah cardiac metabolism study published in Nature.
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