What happens when complex 1 is inhibited?

The inhibition of complex 1 decreases NADH oxidation, proton pumping across the inner mitochondrial membrane and oxygen consumption rate, resulting in lower proton gradient (Δψ) and reduction of proton-driven ATP synthesis from ADP and inorganic phosphate (Pi).

What is the mode of action of rotenone?

Rotenone acts as a strong inhibitor of complex I of the mitochondrial respiratory chain (MRC). The mechanism of action (MOA) comprises inhibition of electron transfer from the iron-sulfur centers in complex I to ubiquinone, leading to a blockade of oxidative phosphorylation with limited synthesis of ATP2.

How does rotenone inhibit electron transport chain?

Rotenone, a botanical pesticide, is an inhibitor of one of the enzymes of Complex I of the electron transport chain. In the presence of this insecticide, electrons from NADH cannot enter the electron transport chain, resulting in the an inability to produce ATP from the oxidation of NADH.

What does Complex 1 do in the electron transport chain?

Complex I is the first enzyme of the respiratory chain. It oxidizes NADH, which is generated through the Krebs cycle in the mitochondrial matrix, and uses the two electrons to reduce ubiquinone to ubiquinol.

How is rotenone used to treat mitochondrial Complex I?

Rotenone was able to induce mitochondrial complex I substrate-supported mitochondrial ROS production both in isolated mitochondria from HL-60 cells as well as in cultured cells. Rotenone-induced apoptosis was confirmed by DNA fragmentation, cytochrome c release, and caspase 3 activity.

What is the mechanism of action of rotenone?

Rotenone acts as a strong inhibitor of complex I of the mitochondrial respiratory chain (MRC). The mechanism of action (MOA) comprises inhibition of electron transfer from the iron-sulfur centers in complex I to ubiquinone, leading to a blockade of oxidative phosphorylation with limited synthesis of ATP 2.

How does rotenone inhibit microtubule assembly and proliferation?

In addition to the effects on the MRC, several studies have demonstrated that rotenone inhibits microtubule assembly independently of a specific energy-requiring step through tubulin binding, resulting in mitotic arrest and inhibition of cell proliferation 5, 6, 7.

Where is rotenone found in the plant roots?

Rotenone is a naturally occurring organic heteropentacyclic compound and member of rotenones that is found in the roots of several plant species. It is a mitochondrial NADH: ubiquinone reductase inhibitor, toxin, and metabolite, and is used as an antineoplastic agent and insecticide.