The "Hole" Story of Cell Suicide
Rice physicist Huey Huang is on a quest to understand death — or at least a little piece of it. Huang has spent the past 15 years studying the properties of cell membranes in an effort to unravel the mystery of cell suicide, a mystery that starts with a tiny hole.
The hole is important because it's a trigger that kicks off a process known as apoptosis. Scientists want to understand apoptosis because of the role it plays — or fails to play — in cancer. In healthy bodies, defective cells are marked for an orderly death by apoptosis. These cells commit suicide and even have the courtesy to package their remains for convenient recycling. Why this happens is a mystery. Cancer cells, however, avoid apoptosis. How they do that is perhaps the bigger mystery, and one reason scientists want to crack the code on apoptosis is to find better ways to fight cancer.
Unfortunately, apoptosis is not well understood. Huang, Rice's Sam and HelenWorden Chair of Physics and Astronomy, opened a leading cell biochemistry textbook to the chapter on apoptosis, which amounted to only a handful of pages. "This is all," he said. "We really understand very little about it."
But breakthroughs in Huang's lab are helping change that. Thanks to Huang, scientists now know the shape of the hole, or pore, that triggers apoptosis. The hole occurs in a membrane that walls off the mitochondria inside a cell.
Themitochondriaare the cell's internal power centers— the places where the cell produces theenergy necessary to live. In cells marked for suicide, an unknown signal creates a protein called Bax that punches the holes, and molecules leak out, kicking off a process that ends with "executioner" proteins systematically dismantling the entire cell.
Knowing that Bax forms pores and understanding how it forms them are two different things. In 1996, Huang and his graduate students proposed a new idea about the way proteins might form pores in the bilayered mitochondrial membranes. They suggested that certain proteins, including Bax, react with the bilayered membrane in such a way as to cause it to curve, forming a rounded hole like the one in a doughnut. Late last year, Huang, his graduate students and his longtime colleague Lin Yang of Brookhaven National Laboratory in Upton, N.Y., used the National Synchrotron Light Source at Brookhaven to take hundreds of painstaking X-ray diffraction images of pores formed by pieces of Bax. They confirmed the toroidal, or doughnut-shaped, hole, settling the debate about how Bax forms holes in membranes.
Huang said the group is now turning its attention to a more difficult investigation. The group is trying to work with the entire Bax protein to find out what causes it to start making holes in the first place.
Thanks to Huang, scientists now know the shape of the hole, or pore, that triggers apoptosis.