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Effect of Acetylation on Energy Sensing Thermostat Protein Molecule

Researchers of National Taiwan University and Johns Hopkins institution have identified the mechanism of an energy sensing “thermostat” protein, which identifies the energy storage or usage in cells.

The study reports that the cell uses energy with a chemical alteration in the thermostat protein, whereas, it stocks up energy when the chemical alteration is absent. Cell death or cancer may occur if the energy is not used effectively.

The researchers studied the enzymes that modify acetyl group in the proteins. Twelve enzymes were considered for the study. For determining the enzyme action on proteins, engineered human cell lines with decreased level of the enzymes were used. In the 12 human lines, 20000 genes were turned down. To find out the effect of the enzymes on the genes, a DNA chip was used. The results from the DNA chip showed that AMP- activated protein kinase (AMPK), the thermostat protein, specifically interacted with HDAC1, an enzyme removing acetyl group.

Normally, AMPK activates the cell to use energy during starvation and slashes down the storage process in the cell. With low amount of HDAC, AMPK was turned off which results in the accumulation of fats and sugars in the cell.

In the study, AMPK was turned on by HDAC1. The researchers suspected the presence of another acetyl-adding enzyme to turn off AMPK. To determine this enzyme, AMPK proteins were extracted from eight cell lines containing low levels of an acetyl adding enzyme. The enzyme was identified to be p300. Low acetylation of AMPK was observed with decreased amount of p300.

The researchers stained the cells for identifying the accumulation of fat globules. This method will show the direct effect of acetyl group on AMPK for energy storage.

The size of the fat globules was determined by using a dye. Larger fat globules were observed on the cells having acetylated AMPK, whereas the fat globules were small on the cells having non acetylated AMPK. This showed that cells store energy with acetylated AMPK when compared to non acetylated AMPK.

Source: http://www.hopkinsmedicine.org/

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