beta(2)-Adrenergic Signaling Modulates Mitochondrial Function and Morphology in Skeletal Muscle in Response to Aerobic Exercise

Author(s)

Azevedo Voltarelli, Vanessa ^[1] ; Coronado, Michael ^[2] ; Goncalves Fernandes, Larissa ^[1] ; Cruz Campos, Juliane ^[3] ; Jannig, Paulo Roberto ^[1] ; Batista Ferreira, Julio Cesar ^{[3, 4]} ; Fajardo, Giovanni ^[2] ; Chakur Brum, Patricia ^[1] ; Bernstein, Daniel ^[2]

Affiliation

^[1] Univ Sao Paulo, Sch Phys Educ & Sport, Dept Biodynam Human Body Movement, BR-05508030 Sao Paulo, SP - Brazil

^[2] Stanford Univ, Sch Med, Dept Pediat, Palo Alto, CA 94304 - USA

^[3] Univ Sao Paulo, Inst Biomed Sci, Dept Anat, BR-05508030 Sao Paulo, SP - Brazil

^[4] Stanford Univ, Sch Med, Dept Chem & Syst Biol, Palo Alto, CA 94304 - USA

• Document type: Journal article
• Source: CELLS; v. 10, n. 1 JAN 2021.
• Web of Science Citations: 0

Abstract

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 beta(2)-adrenergic receptor (beta(2)-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 beta(2)-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 beta(2)-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. beta(2)-AR blockade fully prevented the increase in Mfn1 activity and reduced mitochondrial elongation. To determine the mechanisms involved in mitochondrial modulation by beta(2)-AR activation in skeletal muscle during AE, we used C2C12 myotubes, treated with the non-selective beta-AR agonist isoproterenol (ISO) in the presence of the specific beta(2)-AR antagonist ICI or during protein kinase A (PKA) and G alpha(i) protein blockade. Our in vitro data show that beta-AR activation significantly increases mitochondrial respiration in myotubes, and this response was dependent on beta(2)-AR activation through a G alpha(s)-PKA signaling cascade. In conclusion, we provide evidence for AE-induced beta(2)-AR activation as a major mechanism leading to alterations in mitochondria function and morphology/dynamics. beta(2)-AR signaling is thus a key-signaling pathway that contributes to skeletal muscle plasticity in response to exercise. (AU)

• FAPESP's process: 15/22814-5 - Cancer and heart: new paradigms of diagnosis and treatment
• Grantee: Carlos Eduardo Negrão
• Support Opportunities: Research Projects - Thematic Grants