Effects of Urolithin A on Mitochondrial Homeostasis Disruption by LPS in C2C12 Myotubes

The Toll-like receptor 4 (TLR4) pathway plays a critical role in mediating inflammatory responses and regulates mitochondrial structural adaptations. Urolithin A (UA), a natural compound that induces mito- and autophagy, may improve mitochondrial homeostasis and health. This study examined the effects of UA on TLR4 signaling, mitochondrial dynamics, autophagy, and mitochondrial morphology after lipopolysaccharide (LPS) incubation in C2C12 myotubes.

C2C12 myotubes were incubated with LPS (1 µg/ml) and/or UA (50 µM). Protein expression related to TLR4 signaling, mitochondrial dynamics, and autophagy was assessed by Western blot, while mitochondrial morphology was evaluated using electron microscopy.

LPS-induced inflammation activated downstream TLR4 signaling pathways and altered mitochondrial morphology, including reduced mitochondrial area and circularity. LPS also increased phosphorylation of the mitochondrial fission marker DRP1. UA prevented or attenuated these alterations induced by LPS.

UA partially mitigates LPS-induced inflammation through modulation of TLR4 signaling and mitochondrial dynamics and may represent a promising therapeutic strategy for disorders associated with mitochondrial dysfunction and inflammation.