A few weeks ago I attended my first Gordon Conference on Cell Death in Barga, Italy with my PI, Clay Clark. The conference was located in a beautiful resort nestled in the Tuscan hills off the beaten path between Florence and Pisa. It was a spectacular venue for 170 cell death aficionados to present their most current data and discuss new topics in an informal setting. We arrived in Rome the morning that the conference began, rented a car (we were in line behind Morgan Spurlock) and traversed Italy dodging Italian drivers who have no regard for lanes or speed limits. It is actually a pretty fun experience to drive in Italia! The conference began that evening with two excellent keynote addresses presented by Martin Raff and Richard Youle.
There are a number of processes that lead to the death of a cell: apoptosis, necrosis, and autophagy are the primary mechanisms – each has a distinct biochemical and morphological fingerprint. In a new paper by Brent Stockwell’s lab at Columbia University (1), the term “ferroptosis” is proposed to describe a process of cell death that doesn’t conform to these fingerprints. In this case, cell death results from an iron-dependent accumulation of lipid reactive oxygen species (ROS).
The group previously identified two structurally-unrelated small molecules, erastin (2) and RSL3 (3), that are selectively lethal to RAS mutant cell lines and named these molecules RAS-selective lethal (RSL) compounds. The underlying driving force for these experiments is that RAS family small GTPases are mutated in a large percentage of cancers (~30%), so compounds that are selectively lethal to RAS mutant cells are needed.