TABLE 1.
Comparison between ferroptosis and other types of cell death.
| Type of Cell Death | Definition | Morphological Features | Biochemical Features | Immune Features | Regulatory pathways | Key Genes |
|---|---|---|---|---|---|---|
| Ferroptosis | Non-apoptotic cell death characterized by iron-dependent lipid peroxidation | Small mitochondria with increased mitochondrial membrane densities, reduction or vanishing of mitochondria crista, outer mitochondrial membrane rupture and normal nucleus | Iron accumulation and lipid peroxidation | Promote inflammation | Xc−-GPX4, MVA, HSPB1-TFR1, p62-Keap1-Nrf2, p53-SLC7A11, ATG5-ATG7-NCOA4, p53-SAT1-ALOX15, FSP1-COQ10-NAD(P)H, RPL8, HSPB1, CISD1, LSH, EGLN, FANCD2, CHAC1 | GPX4, TFR1, SLC7A11, Nrf2, NCOA4, p53, HSPB1, ACSL4, FSP1 |
| Apoptosis | Autonomous and orderly death of genetically controlled cells to maintain internal stability | Cellular and nuclear volume reduction, chromatin agglutination, nuclear fragmentation, formation of apoptotic bodies and cytoskeletal disintegration, no significant changes in mitochondrial structure | DNA fragmentation decreases the mitochondrial membrane potential | Inhibit inflammation | Death receptor, mitochondrion and endoplasmic reticulum pathways, caspase, p53, Bcl-2 | Caspase, Bcl-2, Bax, p53, Fas |
| Necroptosis | A mode of cell death that begins with a necrotic phenotype in the form of apoptosis | Plasma membrane break down, generalized swelling of the cytoplasm and organelles, moderate chromatin condensation, spillage of cellular constituents into microenvironment | Enrichment of kinase and drop in ATP level | Promote inflammation | TNF, RIP1/RIP3-MLKL; SIRT5, Toll-like receptors, PKC-MAPK-AP-1, ROS-related metabolic pathway | ATG5, ATG7, LC3, Beclin-1, DRAM3, TFEB |
| Pyroptosis | Pyrooptin-mediated programmed cell necrosis dependent on inflammatory caspase activation | Loss of membrane integrity, loss of organelles DNA condensation and fragmentation | Formation of inflammasomes, activation of caspase-1, release of pro-inflammatory factors | Promote inflammation | Caspase-1, NLRP3-mediated pathway | Caspase-1, IL-1β, IL-18 |
| Autophagy | Under the regulation of related genes, the process by which lysosomes degrade cell’s own damaged organelles and macromolecular substances | Formation of double-membraned autolysosomes, including macro autophagy, micro autophagy, and chaperone-mediated autophagy | Increased lysosomal activity | Promote inflammation | mTOR, Beclin-1, ATG, ULK1, PI3K, p53 | RIP1, RIP3 |