Grefte 2015 Biochim Biophys Acta
| Grefte S, Wagenaars JA, Jansen R, Willems PH, Koopman WJ (2015) Rotenone inhibits primary murine myotube formation via Raf-1 and ROCK2. Biochim Biophys Acta 1853:1606-14. |
Grefte S, Wagenaars JA, Jansen R, Willems PH, Koopman WJ (2015) Biochim Biophys Acta
Abstract: Rotenone (ROT) is a widely used inhibitor of complex I (CI), the first complex of the mitochondrial oxidative phosphorylation (OXPHOS) system. However, particularly at high concentrations ROT was also described to display off-target effects. Here we studied how ROT affected in vitro primary murine myotube formation. We demonstrate that myotube formation is specifically inhibited by ROT (10-100nM), but not by piericidin A (PA; 100nM), another CI inhibitor. At 100nM, both ROT and PA fully blocked myoblast oxygen consumption. Knock-down of Rho-associated, coiled-coil containing protein kinase 2 (ROCK2) and, to a lesser extent ROCK1, prevented the ROT-induced inhibition of myotube formation. Moreover, the latter was reversed by inhibiting Raf-1 activity. In contrast, ROT-induced inhibition of myotube formation was not prevented by knock-down of RhoA. Taken together, our results support a model in which ROT reduces primary myotube formation independent of its inhibitory effect on CI-driven mitochondrial ATP production, but via a mechanism primarily involving the Raf-1/ROCK2 pathway. • Keywords: Fusion index, GW5074, U0126, Rotenone, Piericidin A, Rho-GTPase
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Organism: Mouse
Tissue;cell: Skeletal muscle
Preparation: Permeabilized cells
Regulation: Substrate Coupling state: ROUTINE
HRR: Oxygraph-2k
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