The Life-or-Death Molecule

By Jane Farrell

Researchers have zeroed in on a molecule that’s involved in cell death, a discovery that could lead to better treatment for inflammatory illnesses such as psoriasis, rheumatoid arthritis and Crohn’s disease.

The investigators found that a previously identified molecule, RIPK1, inhibits necroptosis (cell death), which is implicated in inflammatory conditions. Paradoxically, RIPK1 is also responsible for initiating cell death.

 “We showed that, in the body, RIPK1 is not only essential for initiating necroptosis, but also for inhibiting necroptosis and the runaway inflammation that can cause severe tissue damage,” said Associate Professor John Silke, of the Walter and Eliza Hall Institute, Melbourne. “We also found that it played a role in another type of programmed cell death called apoptosis. Our research highlighted that RIPK1 is the gatekeeper that controls whether a cell lives or dies, and the decision it makes on how to die.”

The researchers also said they had shown that RIPK1 has another important role: keeping blood cells alive after a bone marrow transplant.

Necroptosis is a type of ‘controlled’ death that stimulates an inflammatory reaction to let the immune system know something has gone wrong. But when the cell death spins out of control, it can lead to inflammatory disease. Necroptosis has also been implicated in neurodegenerative disease, brain injuries caused by blood loss, and some viral infections.

Silke said necroptosis was a newly discovered type of cell death that had only really been studied in the past five years. “When our time comes to die, we don’t have a choice,” he said. “However, cells make this choice all the time – not only whether they die, but also how they die. They can choose to die quietly, or they can make a fuss. Necroptosis is their way of letting everyone else know that they are dying and help is needed usually when something has gone wrong such as a viral infection.”