Table 1 Distinctions between ferroptosis and apoptosis.
From: Ferroptosis: a double-edged sword mediating immune tolerance of cancer
Forms of RCD | Definition | Characters | Classification | Key molecules | Potential strategies | Targets | Specific targets | Links with immune | References |
|---|---|---|---|---|---|---|---|---|---|
Apoptosis | Programmed cell death, which is an aumomatically cell death pathway determined by genes. | membrane blebbing, cell shrinkage, condensation of chromatin, and fragmentation of DNA | intrinsic apoptotis | Pro-apoptotic BH3-only proteins(BIM, PUMA, BAD or NOXA), pro-survival BCL-2 proteins(BCL-2, BCL-XL, MCL-1 an BCL-2-related protein A1), BAK, BAX, cytochrome c, SMAC, caspase 3, 7 and 9, XIAP, apoptotic peptidase activating factor 1(APAF1). | Strategies targeting intrinsic pathway | BH3 mimetics | Dual BCL-2 and BCL-XL inhibitors | immunologically silent | |
Selective BCL-2 inhibitors | |||||||||
BCL-XL inhibitors | |||||||||
MCL-1 inhibitors | |||||||||
IAP inhibitors and SMAC mimetics | – | ||||||||
extrinsic apoptosis | FAS, FAS ligand(FASL), FADD(FAS associated via death domain), death- inducing signalling complex (DISC), caspase 3, 7 and 8, BH3-only protein BID, tBID. | Strategies targeting extrinsic pathway | Death receptor agonists | – | |||||
Ferroptosis | Ferroptosis is trigged by failure in or blockade of the glutathione-dependent antioxidant defences of a cell, which leads to the unrestrained lipid peroxidation and ultimately the killing of the cell. | presence of smaller than normal mitochondria with condensed mitochondrial membrane densities, reduction or vanishing of mitochondria crista, and outermitochondrial membrane rupture, lipid peroxidation, inactivation of GPX4, iron-dependent | Amino acid metabolism | GPX4, GSH, glutamate, cysteine, glycine, GCL, GSS | Inhibiting ferroptosis | The GPX4-GSH system | Dual role in immune tolerance | [44,45,46,47, 54,55,56,57,58, 60, 61, 63, 65, 66, 178, 238,239,240,241] | |
The FSP1-CoQH2 system | |||||||||
Lipid peroxidation | ASCL4, LPCAT3 | The DHODH-CoQH2 system | |||||||
The GCH1-BH4 system | |||||||||
Iron metabolism | TF, TFR, NCOA4, GOT1 | The FSP1-Vitamin K system | |||||||
Inducing ferroptosis | GSH depleting compounds | ||||||||
Mitochondrial metabolism | AMPK. ACC | GPX4 inhibitors | |||||||
Depletion of GPX4 protein and CoQ10 | |||||||||
Iron oxidation and indirect GPX4 inactivation | |||||||||
