When I last read about cell death it was recognised that there were two basic types, necrosis, that is normal cell death, and apoptosis or programmed cell death. I had heard a little about necroptosis, as it was recently shown to be important in the kidney. I also recognised the name autophagy, but rather thought it was something liver cells did in starvation. It still does, but now it is also a general term for a kind of cell death machinery as well.
It turns out there are now twelve types of regulated cell death (RCD), and even the morphology is no longer any indication of the type of cell death involved. Because, as they write,
"Moreover, each type of RCD can manifest with an entire spectrum of morphological features ranging from fully necrotic to fully apoptotic, and an immunomodulatory profile ranging from anti-inflammatory and tolerogenic to pro-inflammatory and immunogenic."This plethora of mechanisms does rather complicate the understanding of cell death. Especially so as most of the mechanisms can be activated a little bit and then regress, as long as the death threshold has not been reached. And, even more so as they may switch mechanism if you try to intervene against one of the pathways. This is actually one of the major take-home messages of the paper. We have tried a number of different cell death inhibitors that seem to work in experimental systems where the trigger is controlled. However, when we try them out in patients we find that the cells die anyway.
On the other hand, the great number of different mechanisms opens the possibility of an equally great number of new and shiny papers.