Browsing by Author "Gutierrez, Juan"

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    A single bout of resistance exercise triggers mitophagy, potentially involving the ejection of mitochondria in human skeletal muscle
    (2024) Diaz-Castro, Francisco; Tunon-Suarez, Mauro; Rivera, Patricia; Botella, Javier; Cancino, Jorge; Figueroa, Ana Maria; Gutierrez, Juan; Cantin, Claudette; Deldicque, Louise; Zbinden-Foncea, Hermann; Nielsen, Joachim; Henriquez-Olguin, Carlos; Morselli, Eugenia; Castro-Sepulveda, Mauricio
    AimThe present study aimed to investigate the effects of a single bout of resistance exercise on mitophagy in human skeletal muscle (SkM).MethodsEight 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.ResultsOur 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.ConclusionThe 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.