Ulk1 phosphorylation at S555 is not required for endurance training-induced improvements in exercise and metabolic capacity in mice.
J Appl Physiol (1985)
; 137(2): 223-232, 2024 Aug 01.
Article
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| MEDLINE
| ID: mdl-38900860
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.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Condicionamiento Físico Animal
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Músculo Esquelético
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Metabolismo Energético
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Homólogo de la Proteína 1 Relacionada con la Autofagia
Límite:
Animals
Idioma:
En
Revista:
J Appl Physiol (1985)
Asunto de la revista:
FISIOLOGIA
Año:
2024
Tipo del documento:
Article
País de afiliación:
Estados Unidos