Effects of Urolithin A on Mitochondrial Homeostasis Disruption by LPS in C2C12 Myotubes
(2026) Cellular Physiology and Biochemistry — Vol. 60, n° 3, p. 260-269 (2026)
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- Background/Aims: The Toll-like receptor 4 (TLR4) pathway plays a critical role in mediating inflammatory responses and regulates mitochondrial structural adaptations. By inducing mito-and autophagy, urolithin A (UA), a recent natural compound, may potentially enhance mitochondrial homeostasis and health. The aim of this study was to examine the effects of UA on key components and regulators of TLR4 signaling, mitochondrial dynamics and autophagy, and to analyze mitochondrial morphology after lipopolysaccharide (LPS) incubation in C2C12 myotubes. Methods: On day 6 of differentiation, C2C12 myotubes were incubated with LPS (1µg/ml) for 3h and/or UA (50µM) for 24h. Protein expressions associated with TLR4 signaling, mitochondrial dynamics and autophagy were determined by Western blot, and mitochondrial morphology was assessed using electron microscopy. Results: 1) LPS-induced inflammation activated downstream TLR4 signaling, by increasing the expression of inhibitor of nuclear factor-κB (IκBα, p=0.05) and the phosphorylation of extracellular signal-regulated kinase (ERK, p=0.003), p38 (p=0.04) and c-Jun NH(2)-terminal kinase (JNK, p=0.006) and tended to increase the phosphorylation of phospho-transforming growth factor-β-activated kinase 1 (TAK1, p=0.06) and phospho-inhibitor of nuclear factor-κB kinase α/β (IKKαb, p=0.07); 2) LPS reduced mitochondrial area (p=0.05) and circularity (p=0.0004) and tended to reduce mitochondrial perimeter (p=0.07); 3) LPS increased the phosphorylation of the fission marker dynamin-related protein 1 (DRP1, p=0.009); 4) UA completely prevented, or at least attenuated, all previous effects induced by LPS. Conclusion: Our findings suggest that UA partially mitigates LPS-induced inflammation by modulating the TLR4 signaling pathway and Tel. (+32) 10 47 44 43, E-Mail: louise.deldicque@uclouvain.be M.V.-Breton and L. Deldicque contributed equally to this work.
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Tapia-Curimil, G., Valero-Breton, M., & Zbinden-Foncea, H. (2026). Effects of Urolithin A on Mitochondrial Homeostasis Disruption by LPS in C2C12 Myotubes. Cellular Physiology and Biochemistry, 60(3), 260-269. https://doi.org/10.33594/000000869 (Original work published 2026)