Table 1 The main features of ferroptosis, apoptosis, autophagy, necroptosis, and pyroptosis
From: Ferroptosis, a new form of cell death: opportunities and challenges in cancer
Cell death | Ferroptosis | Apoptosis | Autophagy | Necroptosis | Pyroptosis |
|---|---|---|---|---|---|
Biochemical features | Inhibition of xCT and reduced GSH, inhibition of GPX4. Iron accumulation and lipid peroxidation | Activation of caspases oligonucleosomal DNA fragmentation | Increased lysosomal activity | Drop in ATP levels; activation of RIP1, RIP3, and MLKL | Dependent on caspase-1 and proinflammatory cytokine releases |
Morphological features | Small mitochondria with condensed mitochondrial membrane densities, reduction or vanishing of mitochondria crista, as well as outer mitochondrial membrane rupture | Plasma membrane blebbing; cellular and nuclear volume reduction; nuclear fragmentation | Formation of double-membraned autolysosomes | Plasma membrane rupture; organelle swelling; moderate chromatin condensation | Karyopyknosis, cell edema and membrane rupture |
Key genes | GPX4, Nrf2, LSH, TFR1, xCT | Caspase, P53, Fas, Bcl-2, Bax | ATG5, ATG7, DRAM3, TFEB | LEF1, RIP1, RIP3 | Caspase-1, IL-1β, IL-18 |
Regulatory pathways | xCT and Gpx4, MVA, HSF1-HSPB1, p62-Keap1-Nrf2 pathway, LSH signal pathway | Death receptor, Mitochondrial, Endoplasmic reticulum pathway Csapase, P53, Bcl-2 mediated signaling pathway | PI3K-AKT-mTOR,MAPK-ERK1/2-mTOR signal pathway | TNFα,TNFR1,TLR3, TRAIL, FasL, ROS, PKC-MAPK-AP-1-mediated signaling pathway | Caspase-1, NLRP3-mediated signaling pathway. |
Released DAMP | HMGB1 | Ecto-CRT, HMGB1, and ATP | HMGB-1 | DNA and IL-6 | HMGB1, ATP, IL-1β, and IL-18 |
Immune features | Pro-inflammatory | Mostly anti-inflammatory | Mostly anti-inflammatory | Mostly pro-inflammatory | pro-inflammatory |
Inducers | Erastin,DPI2, BSO, SAS, lanperisone, SRS, RSL3, DPI7, DPI10, FIN56, sorafenib, artemisinin | FASL, DCC, UNC5B | Rapamycin, lithium, sodium, valproate, carbamazepine, C2-ceramide, rapamycin | TNFa, zVAD-fmk, PAMPS | ZnO—NPs, Ivermectin |
Inhibitors | Desferoxamine, vitamin E, U0126, ferrostatin-1, SRS, CA-1, cycloheximide, aminooxyacetic acid Liproxstatin-1 HCl | XIAP, c-IAP1, c-IAP2, ILP-2, ML-IAP/livin, NAIP, Z-VADFMK | 3-ME, LY294002, wortmannin, PIK-III, compound 31, SAR 405, Vps34-In1,MRT68921, Spautin-1, Bafilomycin A1, hydrochloroquin | Nec-1, NSA, Kongensin- A | Necrosulfonami-de |