Distinguishing between different forms of non-apoptotic cell death can be challenging, especially as many share similar morphological features. However, the distinct regulatory pathways involved with each provide distinct protein markers that can be used for their detection.

Whether you are looking at necroptosis, pyroptosis or ferroptosis, a combination of different approaches should be used. The study of non-apoptotic cell death should use both specific positive indicators of the cell death mode of interest, coupled with other cell viability assays and techniques to rule out apoptosis.

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Cell death
Cell death happens when a cell fails to maintain essential life functions and can be non-programmed, in the case of injury or trauma, or programmed, as in processes like apoptosis.

Necroptosis
Necroptosis is a programmed form of necrosis that is dependent on activation of receptor-interacting kinase 3 (RIPK3) and the mixed lineage kinase domain-like (MLKL) psuedokinase.

Pyroptosis
Pyroptosis is an inflammatory caspase-dependent form of programmed necrosis that occurs in response to microbial infection.

Ferroptosis
Ferroptosis is another form of programmed non-apoptotic cell death.

Other forms of cell death
Here we describe the other forms of cell death that can occur.

Studying cell death
Distinguishing between different forms of non-apoptotic cell death can be challenging, especially as many share similar morphological features.

General considerations
Points to keep in mind when analyzing more than one parameter to identify which type of cell death we see in the studied cell population.