Table 1.
Comparison of features between apoptosis, autophagy, necroptosis and ferroptosis
Apoptosis | Autophagy | Necroptosis | Ferroptosis | ||
---|---|---|---|---|---|
Morphological features | Cell membrane | Plasma membrane blebbing; rounding-up of the cell | Lack of change | Rupture of plasma membrane | Lack of rupture and blebbing of the plasma membrane; rounding-up of the cell |
Cytoplasm | Retraction of pseudopods; reduction of cellular volume | Accumulation of double-membraned autophagic vacuoles | Cytoplasmic swelling (oncosis); swelling of cytoplasmic organelles | Small mitochondria with condensed mitochondrial membrane densities, reduction or vanishing of mitochondria crista, as well as outer mitochondrial membrane rupture | |
Nucleus | Reduction of nuclear volume; nuclear fragmentation; chromatin condensation | Lack of chromatin condensation | Moderate chromatin condensation | Normal nuclear size and lack of chromatin condensation | |
Biochemical features | Activation of caspases | LC3-I to LC3-II conversion Substrate (e.g., p62) degradation | Drop in ATP levels | Iron and ROS accumulation Activation of MAPKs Inhibition of system Xc - with decreased cystine uptake GSH depletion and increased NAPDH oxidation Release of arachidonic acid mediators (e.g., 11-HETE and 15-HETE) Δψm dissipation | |
Oligonucleosomal DNA fragmentation | Activation of RIP1, RIP3, and MLKL | ||||
Δψm dissipation | Release of DAMPs (e.g., HMGB1) | ||||
PS exposure | PARP1 hyperactivation | ||||
Inhibitors | Caspase inhibitors | Autophagy inhibitors (e.g. 3-MA, wortmannin) | Necrostatins (e.g. Nec-1) | Lipophilic antioxidants (e.g. Fer-1, vitamin E) | |
Necrosulfonamide | Iron chelators (e.g. DFO, CPX) |