Executioner enzyme may short circuit second form of cell death

January 18, 2016

In contrast to apoptosis, necrosis was seen as unregulated death by neglect, until the discovery of an alternative form of cell death, driven by RIP3, called programmed necrosis. This looks like necrosis under the microscope, but like apoptosis is orchestrated by the cell from within rather than occurring because of injury or infection. Mocarski's group recently showed that RIP3 enables cells to sabotage themselves if they are infected by a virus, an activity where apoptosis was once thought to be the most important.

"For several years, the puzzle was: what are the non-apoptotic functions of caspase 8, since there are numerous systems that are impacted by not having it," Mocarski says. "Now we have to consider that the absence of caspase 8 is actually revealing death by RIP3."

Mice lacking both caspase 8 and RIP3 have blood vessels and blood cells that look healthy. However, a few months after birth, they develop swollen lymph nodes, because their white blood cells do not go through apoptosis normally. Other scientists have shown that mice that have caspase 8 missing only in the skin have chronic skin inflammation, a condition resembling eczema in humans.

"Our results indicate that whatever caspase 8 was doing in the skin, removing RIP3 takes care of it," Mocarski says.

Source: Emory University