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New Insights into the Lactate Shuttle: Role of MCT4 in the Modulation of the Exercise Capacity

27 Pages Posted: 26 Jul 2019 Sneak Peek Status: Published

See all articles by Sara Bisetto

Sara Bisetto

Thomas Jefferson University - Department of Pathology, Anatomy and Cell Biology

Megan C. Wright

Arcadia University

Romana A. Nowak

University of Illinois at Urbana-Champaign - Institute for Genomic Biology

Angelo C. Lepore

Thomas Jefferson University

Tejvir S. Khurana

University of Pennsylvania

Emanuele Loro

University of Pennsylvania

Nancy J. Philp

Thomas Jefferson University - Department of Pathology, Anatomy and Cell Biology

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Abstract

Lactate produced by muscle during high intensity activity is an important glycolytic intermediate that supports whole body metabolism. The lactate shuttle model suggest that lactate produced by glycolytic cells is utilized by oxidative ones. MCT4 controls the efflux of lactate from glycolytic muscles. Here we investigated the exercise capacity of mice with disrupted lactate shuttle due to global deletion of MCT4 (MCT4-/-) or muscle-specific deletion of the accessory protein Basigin (iMSBsg-/-). While MCT4-/- and iMSBsg-/- mice have normal muscle morphology and contractility, only MCT4-/- mice exibit a progressive exercise intolerance. In vivo measurements of compound muscle action potentials showed a decrement in the amplitude of the evoked response in the MCT4-/- mice. This reflected in a significant structural degeneration of the neuromuscular junctions (NMJs). We propose that the disruption of the lactate shuttle impacts motor function by destabilizing the motor unit at the level of the NMJ.

Keywords: lactate, MCT4, Exercise, muscle, NMJ, fatigue, Monocarboxylate transporters, lactate shuttle

Suggested Citation

Bisetto, Sara and Wright, Megan C. and Nowak, Romana A. and Lepore, Angelo C. and Khurana, Tejvir S. and Loro, Emanuele and Philp, Nancy J., New Insights into the Lactate Shuttle: Role of MCT4 in the Modulation of the Exercise Capacity (July 26, 2019). Available at SSRN: https://ssrn.com/abstract=3426655 or http://dx.doi.org/10.2139/ssrn.3426655
This is a paper under consideration at Cell Press and has not been peer-reviewed.

Sara Bisetto

Thomas Jefferson University - Department of Pathology, Anatomy and Cell Biology ( email )

United States

Megan C. Wright

Arcadia University

450 S. Easton Road
Glenside, PA Pennsylvania 19038-3295
United States

Romana A. Nowak

University of Illinois at Urbana-Champaign - Institute for Genomic Biology

Urbana, IL 61801

Angelo C. Lepore

Thomas Jefferson University

1015 Walnut St.
Henry Avenue and School House Lane
Philadelphia, PA 19107
United States

Tejvir S. Khurana

University of Pennsylvania

Philadelphia, PA 19104
United States

Emanuele Loro

University of Pennsylvania ( email )

Philadelphia, PA 19104
United States

Nancy J. Philp (Contact Author)

Thomas Jefferson University - Department of Pathology, Anatomy and Cell Biology

United States

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