The different forms of cell death other than ferroptosis include apoptosis, necroptosis, and autophagy. Ferroptosis is distinct from other forms of cell death in several ways.
Biochemical Features
Ferroptosis: Characterized by iron accumulation and lipid peroxidation, leading to damage from iron-dependent reactive oxygen species (ROS).
Apoptosis: Characterized by activation of Caspase pathway, DNA fragmentation, and degradation of mitochondrial transmembrane potential protein
Autophagy: Marked by the presence of autophagosomes, increased lysosomal activity and autophagic flux, and degradation of cytoplasmic components,
Necrosis: Is an unregulated form of cell death and is associated with ATP depletion, hyperactivation of PARP1, and release of damage-associated molecular patterns (DAMPs).
Necroptosis: Involves a fatal influx of Ca2+ and the formation of the RIPK1-RIPK3-MLKL complex.
Pyroptosis: Is caspase-dependent and features formation of inflammasomes and the release of proinflammatory factors.
Morphological Features
Ferroptosis: Cells have shrunken mitochondria with reduced or absent mitochondrial cristae, higher membrane densities, and ruptured outer mitochondrial membranes.
Apoptosis: Cells become shrunken and round with a contracted, invaginated cell membrane, nucleus is condensed and fragmented, and apoptotic bodies are present. Mitochondrial structure remains relatively unaltered with no significant changes.
Autophagy: Involves formation of double-membraned autolysosomes. Displays intact cell membranes with visible autophagosomes and degraded organelles.
Necrosis: Characterized by ruptured cell membranes, swollen cells and organelles, damaged mitochondria, degraded nuclear chromosome, and cell lysis.
Necroptosis: Shows generalized swelling of cytoplasm and organelles, ruptured cell membranes with spillage of cellular constituents, and moderate chromatin condensation.
Pyroptosis: Shows cytoplasmic swelling, fragmented chromatin, shrunken but intact nuclei, and rupture of cell membrane. Mitochondria are intact and swollen with lower matrix density and collapsed cristae.