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Researchers find molecular 'brake' to cell death

a cell needs extra energy from ATP to undergo apoptosis, and that this extra energy was produced from the "pools" of free nucleotides that exist in the cell cytoplasm. Nucleotides are the primary structural chemical units that make up DNA, RNA and proteins, and they combine to play a variety of roles in the cell, such as formation of ATP.

However, through a series of biological and biochemical experiments, Tang and his research team found that adding ATP to a cancer cell could potentially impede apoptosis. They discovered that these nucleotide pools, in fact, act not to promote apoptosis through production of ATP, but to hinder it. They are "pro-survival factors" that prevent CC, when released from the mitochondria, from "seeing" Apaf-1 in the cytoplasm, Tang says.

"When we induced some cell stress and damage, the low levels of CC that came out from the mitochondria were ineffective because they are sequestered by an ocean of free nucleotides and ATP," he says. "No one had ever realized this kind of barrier existed to impede apoptosis."

They found that cell mitochondria needed to release a large and sustained volume of CC to overcome this nucleotide barrier, and they also found evidence that as soon as the release of CC increases, another mechanism kicks in that simultaneously begins to reduce the size of the nucleotide pool to allow CC to bind to Apaf-1, Tang says.

The researchers say this kind of strategy makes sense for the cell, because it acts like a biological fail-safe system to protect against the errant release of CC from malfunctioning mitochondria. A large pool of free nucleotides along with complete ATP molecules normally exists in a healthy cell so that just a little CC could not mistakenly push the cell to self destruct, Tang says. "When CC is still limited in the cell, perhaps through an accidental release, the nucleotide pool will neutralize the CC so that the cell can stay alive," he says. "So, in a way, it takes a
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Source:University of Texas M. D. Anderson Cancer Center


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