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Ulk1 phosphorylation at S555 is not required for endurance training-induced improvements in exercise and metabolic capacity in mice.
- Source :
- Journal of Applied Physiology; Aug2024, Vol. 137 Issue 2, p223-232, 10p
- Publication Year :
- 2024
-
Abstract
- Endurance exercise training improves exercise capacity as well as skeletal muscle and whole body metabolism, which are hallmarks of high quality-of-life and healthy aging. However, its mechanisms are not yet fully understood. Exercise-induced mitophagy has emerged as an important step in mitochondrial remodeling. Unc-51-like autophagy-activating kinase 1, ULK1, specifically its activation by phosphorylation at serine 555, was discovered as an autophagy driver and to be important for energetic stress-induced mitophagy in skeletal muscle, making it a potential mediator of the beneficial effects of exercise on mitochondrial remodeling. Here, we used CRISPR/Cas9-mediated gene editing and generated knock-in mice with a serine-to-alanine mutation of Ulk1 on serine 555. We now report that these mice displayed normal endurance capacity and cardiac function at baseline with a mild impairment in energy metabolism as indicated by an accelerated increase of respiratory exchange ratio (RER) during acute exercise stress; however, this was completely corrected by 8 wk of voluntary running. Ulk1-S555A mice also retained the exercise-mediated improvements in exercise capacity and metabolic flux. We conclude that Ulk1 phosphorylation at S555 is not required for exercise-mediated improvements of exercise and metabolic capacity in healthy mice. NEW & NOTEWORTHY: We have used CRISPR/Cas9-mediated gene editing to generate Ulk1-S555A knock-in mice to show that loss of phosphorylation of Ulk1 at S555 blunted exercise-induced mitophagy and mildly impairs energy metabolism during exercise in healthy mice. However, the knock-in mice retained exercise training-mediated improvements of endurance capacity and energy metabolism during exercise. These findings suggest that exercise-induced mitophagy through Ulk1 activation is not required for the metabolic adaptation and improved exercise capacity in young, healthy mice. [ABSTRACT FROM AUTHOR]
- Subjects :
- AEROBIC capacity
EXERCISE physiology
PHOSPHORYLATION
MICE
GENOME editing
Subjects
Details
- Language :
- English
- ISSN :
- 87507587
- Volume :
- 137
- Issue :
- 2
- Database :
- Complementary Index
- Journal :
- Journal of Applied Physiology
- Publication Type :
- Academic Journal
- Accession number :
- 179461223
- Full Text :
- https://doi.org/10.1152/japplphysiol.00742.2023