Table 1.
Comparison of different types of cell death
| Types of cell death | Biochemical features |
Morphological features |
Immune features | Regulatory Pathways | Key genes |
|---|---|---|---|---|---|
| Ferroptosis | Inhibition of Xc- and GPX4, reduced GSH, Iron accumulation and lipid peroxidation | Small mitochondria with condensed mitochondrial membrane densities, reduction or vanishing of mitochondria crista, as well as outer mitochondrial membrane rupture. |
Pro-inflammatory | System Xc-/GPX4, MVA, HSF1/HSPB1, p62/Keap1/Nrf2 | GPX4, SLC7A11, Nrf2, ACSL4, FSP1 |
| Ferritinophagy | Increased lysosomal activity, iron accumulation and lipid peroxidation |
Mitochondria atrophy, chromatin concentration, organelle swelling, plasma membrane rupture, formation of double-membraned autolysosomes. | Pro-inflammatory | Iron homeostasis disorder, ROS, ATG12/ATG5/LC3 | NCOA4, ATG5, ATG7, LC3B, FTH1, SOD2, SOX4 |
| Cuproptosis | Cu2+ overload triggers disruption of iron-sulfur cofactors; excessive ROS; Cu depedent-, mitochondria- induced cell death |
Reduction of mitochondria volume and cristae; increased density of bilayer membrane structure. |
Pro-inflammatory | TCA cycle, ROS, mitochondrial respiration, copper homeostasis disorder |
DLAT, PDHA1, PDHB, SLC25A3, FDX1, LIAS, HSP70 |
| Apoptosis | DNA fragmentation decreases the mitochondrial membrane potential | Plasma membrane blebbing, cellular and nuclear volume reduction, nuclear fragmentation. | Anti-inflammatory | Death receptor, mitochondria and endoplasmic reticulum pathway, caspase, p53, Bcl-2 | Caspases, Bcl-2, Bax, p53, Fas |
| Necroptosis | Activation of kinases and drop in ATP levels | Plasma membrane rupture, organelle swelling, moderate chromatin condensation |
Pro-inflammatory | TNF-α, TNFR1, TLR3, TRAIL, FasL, ROS, PKC/MAPK/AP-1 | LEF1, RIP1, RIP3 |
| Pyroptosis | Dependent on caspase-1 and proinflammatory cytokine releases | Karyopyknosis, cell edema and membrane rupture. | Pro-inflammatory | Caspase-1, NLRP3-mediated signaling pathway | Caspase-1, IL-1β, IL-18 |
| Autophagy | Increased lysosomal activity |
Formation of double-membraned autolysosomes. | Anti-inflammatory | PI3K/AKT/mTOR, MAPK/ERK1/2/ mTOR signaling pathway |
ATG5, ATG7, LC3, DRAM3, TFEB |
ACSL4: acyl-CoA synthetase long-chain family member 4, ALOX-15: arachidonate lipoxygenase 15, AP-1: activator protein-1, ATG5: autophagy-related 5, ATG7: autophagy-related 7, COQ10: coenzyme Q10, DRAM3: damage regulated autophagy modulator 3, FSP1: ferroptosis suppressor protein 1, GPX4: glutathione peroxidase 4, HSPB1: heat shock protein beta-1, Keap1: Keleh-like ECH-associated protein 1, MAPK: mitogen-activated protein kinase, MLKL: mixed lineage kinase domain like protein, mTOR: mammalian target of rapamycin, MVA: mevalonate, LC3: microtubule-associated protein 1 light chain 3, NCOA4: nuclear receptor coactivator 4, Nrf2: nuclear factor erythroid 2-related factor 2, PKC: protein kinase C, RIP: receptor-interacting serine/threonine kinase, ROS: reactive oxygen species, SAT1: spermidine/spermine N1-acetyltransferase 1, SLC7A11: solute carrier family 7 member 11, system Xc-: cysteine/glutamate transporter receptor, TFEB: transcription factor EB, TFR1: transferrin receptor 1, TNF-α: tumor necrosis factor α, TCA cycle: tricarboxylic acid cycle.