TABLE 1.

Characteristics of ferroptosis, apoptosis, autophagy, pyroptosis and necroptosis

	Ferroptosis	Apoptosis	Autophagy	Pyroptosis	Necroptosis
Discovery time	2012	1972	1992	2009	2005
Discoverer	Scott J. Dixon, USA	John F R Kerr, Andrew H Wyllie and Alastair R Currie, UK	Yoshinori Ohsumi, Japan	Tessa Bergsbaken, USA	Alexei Degterev, USA
Morphology	Round, shrunken and dwindled‐sized mitochondria Increased mitochondrial membrane density Reduction or loss of mitochondrial crista and outer membrane Structural damage in mitochondria and nucleus	Cellular and nuclear pycnosis Chromatin agglutination No significant damage in the integrity of cellular membrane Formation of apoptotic bodies	Formation of autophagosmes and autolysosomes Swell of endoplasmic reticulum, Golgi body and mitochondria	Cellular swell Chromatin condensation Cell and organelle membrane disruption Aqtocytolysis	Cellular swell Chromatin condensation Cell and organelle membrane disruption Aqtocytolysis
Biochemistry	Iron accumulation Lipid peroxidation Feton reaction Cystine deprivation	ATP‐dependent Regular DNA fragmentation Ca2+ overload Endonuclease activation	Lysosomal activation ATGs activation mTOR inhibition	NLRP3 activation ROS production Lysosomal disruption Potassium efflux	ATP‐independent Irregular DNA fragmentation
Key genes	GPX4, ACSL4, TFRC, SLC7A11, SLC3A2, FSP1, ATM, MTF1, FPN1, NRF2, NCOA4, HSPB1, LPCAT3, ALOX12/15, JNK, p38, p53, NOXs, ATGs	Caspase‐3, Bcl‐2, Bak, Bax, Fas, ASK1, JNK, p38, p53	ATGs, LC3, Beclin‐1, p62/SQSTM1, mTOR, AMPK, PI3K, VPS34, DRAM3, TFEB	Inflammatory caspase family, NLR family, Gasdermin family, NLRP1/3, p10, IL‐1β, IL‐18	RIPK1, RIPK3, MLKL, TNFR1, Fas, TRADD, NOXs, RFK, HMOX‐1, TLR4, JNK
Regulatory mechanisms	System Xc− Mevalonate pathway IRP1/IRP2 ATG5/ATG7/NCOA4 Mitochondrial GLS2/glutaminolysis Sulfasalazine transferation p62/Keap1/NRF2 RSL3 mechanisms, HSPB1‐TRF1 Peroxidation of PUFA‐PLs p53/SAT1/ALOX15 Amino acid starvation FSP1‐COQ10‐NAD(P)H	MAPK/ERK IKK/IKB/NF‐κB IFN‐mediated JAK–STAT PI3K/Akt/mTOR Caspase‐3 pathway Bcl‐2 pathway Bak/Bax pathway p38 pathway Hippo pathway	PI3K/Akt/mTOR AMPK/mTOR A2AR/SIRT3/AMPK JAK/STAT3/SIRT1 Akt/Nrf2 NF‐κB pathway Notch pathway p53 pathway	Inflammatory caspase family pathway NLRP1/3 pathway Gasdermin family pathway HMGB1/RAGE/cathespin B pathway BAK/BAX‐caspase‐3‐GSDME pathway p38/MAPK pathway IL‐1β/IL‐18 pathway	JAK/STAT1/IRF1 PKC/MAPK/AP‐1 RIP1/RIP3/MLKL Ripk3/Pgam5 ROS‐related pathway MYC‐mediated pathway JNK pathway
Inducers	Erastin, Piperazine erastin, Imidazole ketone erastin, RSL3, Sorafenib, Sulfasalazine, Iron, Cyst(e)inase, DPI family, FIN56, FINO2, Artesunate, Cisplatin, Doxorubicin	Various drugs or compounds and diseases	Rapamycin, MG‐132, SB 203580, Cisplatin, Sorafenib, Olaparib	Inflammatory caspase family, Gasdermin family, Cisplatin, Metformin, Anthocyanin, DHA, Paclitaxel	Sorafenib, Artesunate, Shikonin, 5‐FU, Iron, Resibufogenin, Doxorubicin
Inhibitors	Ferrostatin‐1, Deferoxamine, Deferiprone, Ciclopirox, β‐mercaptoethanol, Cycloheximide, Liproxststatin‐1, Vitamin E, SRS11‐9, SRS16‐86, U0126	Caspase family inhibitors	3‐Methyladenine, Chloroquine, Cycloheximide, Bafilomycin A1, Resatorvid	Inflammatory caspase family inhibitors, Gasdermin family inhibitors	Necrostatin‐1

Abbreviations: ACSL4, acyl‐CoA synthetase long‐chain family member 4; ALOX12/15, arachidonate lipoxygenase 15; ATGs, autophagy‐related genes; COQ10, coenzyme Q10; ERK, extracellular signal‐regulated kinase; FSP1, ferroptosis suppressor protein 1; GPX4, glutathione peroxidase 4; HSPB1, heat shock protein family B (small) member 1; IRP1 and IRP2, iron‐regulatory proteins 1 and 2; Keap1, kelch‐like ECH‐associated protein 1; LPCAT3, lysophosphatidylcholine acyltransferase 3; MAPK, mitogen‐activated protein kinase; mTOR, mammalian target of rapamycin; NCOA4, nuclear receptor coactivator; NRF2, nuclear factor erythroid 2‐related factor4; PUFA‐PLs, polyunsaturated‐fatty‐acid–containing phospholipids; RSL3, RAS synthetic lethal 3.