Table 1.
Characteristics of autophagy and ferroptosis.
| Autophagy | Ferroptosis | |
|---|---|---|
| Presented time | 1963 | 2012 |
| Definition | Autophagy is a highly conserved self-digestion process. | Ferroptosis is an iron-dependent form of regulated cell death. |
| Morphological characteristics | Autophagosomes, a double membrane vesicle containing multiple cytoplasmic contents. The autophagosomes fuse with lysosomes to form autolysosomes. |
Atrophy of mitochondria with increased membrane densities, reduced even disappeared mitochondria crista and ruptured outer membrane, normal nucleus |
| Mechanisms | Initiation and nucleation, maturation of autophagosomes and fusion with the lysosome and degradation. Controlled by Atgs and several complicated signaling pathways. | Iron overload, GSH depletion and GPX 4 inactivation, impaired system Xc-, lipid peroxidation. |
| Key regulators | AMPK,mTOR,Beclin1, PI3K,ULK1,P62,P53,STAT3 and other Atgs | Positive:ACSL4,TfR1, LPCAT3, ALOX15, NCOA4, Beclin1, GLS2, VDAC2/3, RAB7A, P53 and HSP90 Negative:GPX4,SLC7A11, Nrf2, HSPB1, HSPA5, P53, NFS1 and OTUB1 |
| Inducers | Simvastatin, Rapamycin, Metformin, Resveratrol, sodium,Everolimus,Brefeldin A | Erastin, Sorafenib, Glutamate, Artesunate, RSL3, FIN56, FINO2, iFSP1, Fluvastatin, Hemoglobin |
| Inhibitors | 3-MA,LY294002,SBI-0206965,NSC185058, Chloroquine, Compound C, Nocodazole, Bafilomycin A1, Pepstatin A, Spautin-1,Hydroxychloroquine | Deferoxamine, Vitamin E, Ferrostatin-1, Liproxstatin-1, CoQ10, Baicalein, GSH, Rosiglitazone, Selenium |
AMPK, Adenosine 5′-monophosphate (AMP)-activated protein kinase; PI3K, Phosphatidylinositol 3-kinase; ULK1, unc-51-like kinase 1; STAT3, Signal transducer and activator of transcription 3; Atgs, Autophagy-related genes; RSL3, Ras-selective lethal small molecule 3; iFSP1, inhibitor of FSP1; GSH, Glutathione; ACSL4, Acyl-CoA synthetase long chain family member 4; TfR1, Transferrin receptor 1; LPCAT3, Lysophosphatidylcholine acyltransferase 3; ALOX15, Arachidonate-15-Lipoxygenase; NCOA4, Nuclear receptor coactivator 4; GLS2, Glutaminase 2; VDAC, voltage-dependent anion channels; HSP90, Heat shock protein 90; GPX4, Glutathione peroxidase 4;;SLC7A11, solute carrier family 7 member 11; Nrf2, nuclearfactorerythroid-2-relatedfactor2; HSPA5, Heat shock 70 kDa protein 5; NFS1, Cysteine desulfurase; OTUB1, ovarian tumor family member deubiquitinase; 3-MA, 3-Methyladenine.