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Rotenone is an inhibitor of the mitochondrial complex I electron transport chain with IC50 value of 1.7 - 2.2 μM.

Electron transport chain (ETC) is a series of compounds that transfer electrons from electron donors to electron acceptors and transfer protons (H+ ions) across a membrane. The proton gradient drives ATP synthesis. Complex I is one of the main sites of production of superoxide.

Rotenone is an inhibitor of the mitochondrial complex I electron transport chain. In the transformed cell line HEK 293 and cancer cell lines U87, rotenone (50 μM) induced cell death by 30% and 40% respectively in a dose dependent way, which was mediated by reactive oxygen species (ROS). Also, rotenone significantly induced autophagy formation [1]. In SH-SY5Y cells, rotenone induced cell apoptosis in a caspase-dependent way. Also, rotenone induced phosphorylation of p38 MAP kinase, c-Jun and JNK, which indicated activation of the p38 and JNK pathways [2]. In differentiated SH-SY5Y neuroblastoma cells, rotenone (50 nM) induced cell death by 60% and slowed mitochondrial movement. While rotenone didn’t induce the formation of resembling Lewy bodies [3].

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