Mitochondrial Complex I Inhibitor Rotenone Induces Apoptosis through Enhancing Mitochondrial Reactive Oxygen Species Production

References

Li, Nianyu , Kathy  Ragheb, and Gretchen  Lawler. “Mitochondrial Complex I Inhibitor Rotenone Induces Apoptosis through Enhancing Mitochondrial Reactive Oxygen Species Production.” The Journal Of Biological Chemistry 278, no. 10 (2003): 8516-8525. Accessed April 13, 2013. http://www.jbc.org/content/278/10/8516.full#sec-22

 PUBLISHED PAPER 2

Rotenone inhibits complex 1 in the electron transport chain (ETC) and has leads to the death of a number of cells. The reactive oxygen species (ROS) aids in apoptosis and the inhibiting of complex 1 by rotenone promotes the creation of ROS. Rotenone along with the increased ROS generates a similar substrate to complex 1 substrate. DNA fragmentation was able to determine that apoptosis, the release of cytochrome c and caspase is caused by rotenone. Apoptosis caused by rotenone can be stopped using antioxidants. In apoptosis, magnesium superoxide dismutase is resilient to rotenone-induced mitochondrial ROS.

 

Complex 1- 4 and ATP synthase in the ETC produces ATP as well as assist in apoptosis of the cell due to the ROS. Mitochondria discharge a number of proapoptotic regulators such as cytochrome c to the cytosol when the apoptosis process is stimulate. The regulators triggers the apoptotic process, as well as it is controlled by proteins and results in the mitochondria being the central path of apoptosis signal.

 

The significance of rotenone-induced apoptosis was determined with a tumor necrosis factor (TNF)-α which can disrupt complex 1 in ETC while other intelligences state that rotenone can inhibit cells outside the mitochondria.

 

ROS is suspected to be activated by several other molecules within the body including UV radiation. ETC produces the main supply of ROS under biological conditions and hence it is been thought that ROS formed from the mitochondria contributes to the apoptosis process. The ROS mitochondria manipulate the mitochondria functioning exclusive of the cytosol, two complexes in the ETC, complex 1 and 3 are also known to be contributors of ROS

 

From chemical determination superoxide and hydrogen peroxide was determined to be primary and secondary products and it has been noted that rotenone as well as complex b-c1 inhibitor antimycin can cause the formation of both oxides. The ROS made in the mitochondria can be altered when inhibition takes place.

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