The Protein Orchestrating Cells’ Dance of Death

When cells become diseased or infected, a “suicide switch” is triggered, preventing neighboring cells from becoming compromised. This self-destructive process, known as necroptosis, is tightly controlled by a complex network of biochemical pathways. However, certain conditions, such as inflammatory bowel disease, can see necroptosis spiraling out of control with major health consequences. Molecular targets for managing this uncontrolled cell death have so far remained elusive — until now.

A multidisciplinary team of scientists has recently made a huge leap in advancing our understanding of necroptosis, shedding light on a protein controller of cell death called MLKL. In a series of three concurrent publications, scientists from the Australian Walter and Eliza Hall Institute describe critical new insights on the structure, function, and evolutionary origins of MLKL. Significantly, they also reveal never-before-seen links between subtle mutations in MLKL and their effects on human inflammatory disease.

Using a suite of high-resolution imaging techniques, the researchers were able to watch MLKL in action during the cell’s final act. As study investigator Andre Samson describes, “We could see how MLKL changed its location as necroptosis occurred, clumping and migrating to different parts of the cell as the cell progressed towards death.”