New Insights into the Lactate Shuttle: Role of MCT4 in the Modulation of the Exercise Capacity
Summary: Lactate produced by muscle during high-intensity activity is an important end product of glycolysis that supports whole body metabolism. The lactate shuttle model suggested that lactate produced by glycolytic muscle fibers is utilized by oxidative fibers. MCT4 is a proton coupled monocarbox...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2019-12-01
|
| Series: | iScience |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004219304924 |
| _version_ | 1818033075403096064 |
|---|---|
| author | Sara Bisetto Megan C. Wright Romana A. Nowak Angelo C. Lepore Tejvir S. Khurana Emanuele Loro Nancy J. Philp |
| author_facet | Sara Bisetto Megan C. Wright Romana A. Nowak Angelo C. Lepore Tejvir S. Khurana Emanuele Loro Nancy J. Philp |
| author_sort | Sara Bisetto |
| collection | DOAJ |
| description | Summary: Lactate produced by muscle during high-intensity activity is an important end product of glycolysis that supports whole body metabolism. The lactate shuttle model suggested that lactate produced by glycolytic muscle fibers is utilized by oxidative fibers. MCT4 is a proton coupled monocarboxylate transporter preferentially expressed in glycolytic muscle fibers and facilitates the lactate efflux. 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−/−). Although MCT4−/− and iMSBsg−/− mice have normal muscle morphology and contractility, only MCT4−/− mice exhibit an exercise intolerant phenotype. In vivo measurements of compound muscle action potentials showed a decrement in the evoked response in the MCT4−/− mice. This was accompanied by a significant structural degeneration of the neuromuscular junctions (NMJs). We propose that disruption of the lactate shuttle impacts motor function and destabilizes the motor unit. : Musculoskeletal Medicine; Genetics; Neuroscience Subject Areas: Musculoskeletal Medicine, Genetics, Neuroscience |
| first_indexed | 2024-12-10T06:17:30Z |
| format | Article |
| id | doaj.art-ce448164eafd4ade9a76cd5e99222414 |
| institution | Directory Open Access Journal |
| issn | 2589-0042 |
| language | English |
| last_indexed | 2024-12-10T06:17:30Z |
| publishDate | 2019-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj.art-ce448164eafd4ade9a76cd5e992224142022-12-22T01:59:25ZengElsevieriScience2589-00422019-12-0122507518New Insights into the Lactate Shuttle: Role of MCT4 in the Modulation of the Exercise CapacitySara Bisetto0Megan C. Wright1Romana A. Nowak2Angelo C. Lepore3Tejvir S. Khurana4Emanuele Loro5Nancy J. Philp6Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, Philadelphia, PA 19107, USADepartment of Biology, Arcadia University, Glenside, PA 19038, USAInstitute for Genomic Biology, University of Illinois, Urbana, IL 61801, USADepartment of Neuroscience, Thomas Jefferson University, Philadelphia, PA 19107, USADepartment of Physiology and Pennsylvania Muscle Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USADepartment of Physiology and Pennsylvania Muscle Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Corresponding authorDepartment of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, Philadelphia, PA 19107, USA; Corresponding authorSummary: Lactate produced by muscle during high-intensity activity is an important end product of glycolysis that supports whole body metabolism. The lactate shuttle model suggested that lactate produced by glycolytic muscle fibers is utilized by oxidative fibers. MCT4 is a proton coupled monocarboxylate transporter preferentially expressed in glycolytic muscle fibers and facilitates the lactate efflux. 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−/−). Although MCT4−/− and iMSBsg−/− mice have normal muscle morphology and contractility, only MCT4−/− mice exhibit an exercise intolerant phenotype. In vivo measurements of compound muscle action potentials showed a decrement in the evoked response in the MCT4−/− mice. This was accompanied by a significant structural degeneration of the neuromuscular junctions (NMJs). We propose that disruption of the lactate shuttle impacts motor function and destabilizes the motor unit. : Musculoskeletal Medicine; Genetics; Neuroscience Subject Areas: Musculoskeletal Medicine, Genetics, Neurosciencehttp://www.sciencedirect.com/science/article/pii/S2589004219304924 |
| spellingShingle | Sara Bisetto Megan C. Wright Romana A. Nowak Angelo C. Lepore Tejvir S. Khurana Emanuele Loro Nancy J. Philp New Insights into the Lactate Shuttle: Role of MCT4 in the Modulation of the Exercise Capacity iScience |
| title | New Insights into the Lactate Shuttle: Role of MCT4 in the Modulation of the Exercise Capacity |
| title_full | New Insights into the Lactate Shuttle: Role of MCT4 in the Modulation of the Exercise Capacity |
| title_fullStr | New Insights into the Lactate Shuttle: Role of MCT4 in the Modulation of the Exercise Capacity |
| title_full_unstemmed | New Insights into the Lactate Shuttle: Role of MCT4 in the Modulation of the Exercise Capacity |
| title_short | New Insights into the Lactate Shuttle: Role of MCT4 in the Modulation of the Exercise Capacity |
| title_sort | new insights into the lactate shuttle role of mct4 in the modulation of the exercise capacity |
| url | http://www.sciencedirect.com/science/article/pii/S2589004219304924 |
| work_keys_str_mv | AT sarabisetto newinsightsintothelactateshuttleroleofmct4inthemodulationoftheexercisecapacity AT megancwright newinsightsintothelactateshuttleroleofmct4inthemodulationoftheexercisecapacity AT romanaanowak newinsightsintothelactateshuttleroleofmct4inthemodulationoftheexercisecapacity AT angeloclepore newinsightsintothelactateshuttleroleofmct4inthemodulationoftheexercisecapacity AT tejvirskhurana newinsightsintothelactateshuttleroleofmct4inthemodulationoftheexercisecapacity AT emanueleloro newinsightsintothelactateshuttleroleofmct4inthemodulationoftheexercisecapacity AT nancyjphilp newinsightsintothelactateshuttleroleofmct4inthemodulationoftheexercisecapacity |