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Open AccessArticle

β2-Adrenergic Signaling Modulates Mitochondrial Function and Morphology in Skeletal Muscle in Response to Aerobic Exercise

1
Department of Biodynamics of the Human Body Movement, School of Physical Education and Sport, University of São Paulo, São Paulo 05508-030, SP, Brazil
2
Department of Pediatrics, School of Medicine, Stanford University, Palo Alto, CA 94304, USA
3
Department of Anatomy, Institute of Biomedical Sciences, University of São Paulo, São Paulo 05508-030, SP, Brazil
4
Department of Chemical and Systems Biology, School of Medicine, Stanford University, Palo Alto, CA 94304, USA
*
Authors to whom correspondence should be addressed.
Equal contribution of senior authors.
Cells 2021, 10(1), 146; https://doi.org/10.3390/cells10010146
Received: 24 November 2020 / Revised: 28 December 2020 / Accepted: 11 January 2021 / Published: 13 January 2021
(This article belongs to the Special Issue Mitochondrial Dysfunction in Degenerative Diseases)
The molecular mechanisms underlying skeletal muscle mitochondrial adaptations induced by aerobic exercise (AE) are not fully understood. We have previously shown that AE induces mitochondrial adaptations in cardiac muscle, mediated by sympathetic stimulation. Since direct sympathetic innervation of neuromuscular junctions influences skeletal muscle homeostasis, we tested the hypothesis that β2-adrenergic receptor (β2-AR)-mediated sympathetic activation induces mitochondrial adaptations to AE in skeletal muscle. Male FVB mice were subjected to a single bout of AE on a treadmill (80% Vmax, 60 min) under β2-AR blockade with ICI 118,551 (ICI) or vehicle, and parameters of mitochondrial function and morphology/dynamics were evaluated. An acute bout of AE significantly increased maximal mitochondrial respiration in tibialis anterior (TA) isolated fiber bundles, which was prevented by β2-AR blockade. This increased mitochondrial function after AE was accompanied by a change in mitochondrial morphology towards fusion, associated with increased Mfn1 protein expression and activity. β2-AR blockade fully prevented the increase in Mfn1 activity and reduced mitochondrial elongation. To determine the mechanisms involved in mitochondrial modulation by β2-AR activation in skeletal muscle during AE, we used C2C12 myotubes, treated with the non-selective β-AR agonist isoproterenol (ISO) in the presence of the specific β2-AR antagonist ICI or during protein kinase A (PKA) and Gαi protein blockade. Our in vitro data show that β-AR activation significantly increases mitochondrial respiration in myotubes, and this response was dependent on β2-AR activation through a Gαs-PKA signaling cascade. In conclusion, we provide evidence for AE-induced β2-AR activation as a major mechanism leading to alterations in mitochondria function and morphology/dynamics. β2-AR signaling is thus a key-signaling pathway that contributes to skeletal muscle plasticity in response to exercise. View Full-Text
Keywords: aerobic exercise; mitochondria; β2-adrenoceptor; sympathetic nervous system; skeletal muscle aerobic exercise; mitochondria; β2-adrenoceptor; sympathetic nervous system; skeletal muscle
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MDPI and ACS Style

Azevedo Voltarelli, V.; Coronado, M.; Gonçalves Fernandes, L.; Cruz Campos, J.; Jannig, P.R.; Batista Ferreira, J.C.; Fajardo, G.; Chakur Brum, P.; Bernstein, D. β2-Adrenergic Signaling Modulates Mitochondrial Function and Morphology in Skeletal Muscle in Response to Aerobic Exercise. Cells 2021, 10, 146. https://doi.org/10.3390/cells10010146

AMA Style

Azevedo Voltarelli V, Coronado M, Gonçalves Fernandes L, Cruz Campos J, Jannig PR, Batista Ferreira JC, Fajardo G, Chakur Brum P, Bernstein D. β2-Adrenergic Signaling Modulates Mitochondrial Function and Morphology in Skeletal Muscle in Response to Aerobic Exercise. Cells. 2021; 10(1):146. https://doi.org/10.3390/cells10010146

Chicago/Turabian Style

Azevedo Voltarelli, Vanessa; Coronado, Michael; Gonçalves Fernandes, Larissa; Cruz Campos, Juliane; Jannig, Paulo R.; Batista Ferreira, Julio C.; Fajardo, Giovanni; Chakur Brum, Patricia; Bernstein, Daniel. 2021. "β2-Adrenergic Signaling Modulates Mitochondrial Function and Morphology in Skeletal Muscle in Response to Aerobic Exercise" Cells 10, no. 1: 146. https://doi.org/10.3390/cells10010146

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