A single bout of resistance exercise triggers mitophagy, potentially involving the ejection of mitochondria in human skeletal muscle.
(2024) Acta physiologica — Vol. 240, n° 9, p. e14203 [1-15] (2024)
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Díaz-Castro, Francisco 
Tuñón-Suárez, Mauro Castro-Sepúlveda, Mauricio
- Abstract
- (en) AIM: The present study aimed to investigate the effects of a single bout of resistance exercise on mitophagy in human skeletal muscle (SkM). METHODS: Eight healthy men were recruited to complete an acute bout of one-leg resistance exercise. SkM biopsies were obtained one hour after exercise in the resting leg (Rest-leg) and the contracting leg (Ex-leg). Mitophagy was assessed using protein-related abundance, transmission electron microscopy (TEM), and fluorescence microscopy. RESULTS: Our results show that acute resistance exercise increased pro-fission protein phosphorylation (DRP1Ser616) and decreased mitophagy markers such as PARKIN and BNIP3L/NIX protein abundance in the Ex-leg. Additionally, mitochondrial complex IV decreased in the Ex-leg when compared to the Rest-leg. In the Ex-leg, TEM and immunofluorescence images showed mitochondrial cristae abnormalities, a mitochondrial fission phenotype, and increased mitophagosome-like structures in both subsarcolemmal and intermyofibrillar mitochondria. We also observed increased mitophagosome-like structures on the subsarcolemmal cleft and mitochondria in the extracellular space of SkM in the Ex-leg. We stimulated human primary myotubes with CCCP, which mimics mitophagy induction in the Ex-leg, and found that BNIP3L/NIX protein abundance decreased independently of lysosomal degradation. Finally, in another human cohort, we found a negative association between BNIP3L/NIX protein abundance with both mitophagosome-like structures and mitochondrial cristae density in the SkM. CONCLUSION: The findings suggest that a single bout of resistance exercise can initiate mitophagy, potentially involving mitochondrial ejection, in human skeletal muscle. BNIP3L/NIX is proposed as a sensitive marker for assessing mitophagy flux in SkM.
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Díaz-Castro, F., Tuñón-Suárez, M., Rivera, P., Botella, J., Cancino, J., Figueroa, A. M., Gutiérrez, J., Cantin, C., Deldicque, L., Zbinden-Foncea, H., Nielsen, J., Henríquez-Olguín, C., Morselli, E., & Castro-Sepúlveda, M. (2024). A single bout of resistance exercise triggers mitophagy, potentially involving the ejection of mitochondria in human skeletal muscle. Acta physiologica, 240(9), e14203 [1-15]. https://doi.org/10.1111/apha.14203 (Original work published 2024)