Table1 Comparison of multiple forms of cell death

Initiators

Loss of growth factor signals, DNA damage, reactive oxygen species (ROS) excess, hypoxia, chemotherapeutic medicines

Extracellular microenvironment, TNF-α, FasL (death ligand binds its receptor), and infectious pathogens

Toxins, infections, trauma

Ischemic injury,

FASL, TNFR1

Erastin, RSL3, iron accumulation and lipid peroxidation,

LPS, DAMPs, microbial infections

[18, 23,24,25, 34, 41, 190,191,192]

Intermediate signalings

Mitochondrial pathway Caspase-3, -6, -7, -9-dependent

Caspase-3, -8-dependent

Danger signals, ROS

Caspase-independent RIP1/RIP3/MLKL necrosome

Iron-dependent production of ROS

Nod-like receptors (NLRP3) Caspase 1-dependent pyroptosome, caspase-4/5/11

[193]

Morphological features

Retention of plasma membrane integrity, cell shrinkage, DNA fragmentation, phosphatidylserine (PS) exposure, and the formation of apoptotic bodies

Retention of plasma membrane integrity, cell shrinkage, DNA fragmentation, phosphatidylserine (PS) exposure, and the formation of apoptotic bodies

Loss of plasma membrane integrity, cell swelling, leak of content

Membrane permeabilization, swollen cellular organelles

Cytoplasmic swelling (oncosis), chromatin condensation, swelling of cytoplasmic organelles and loss of membrane integrity

Pore formation, swelling of cell, rapid loss of plasma membrane

[56, 194,195,196,197,198]

DAMPs released

CRT, ATP (at pre-apoptotic stage), HMGB1(at late-apoptotic stage), histones,

Annexin A1 (ANXA1)

CRT, ATP, HMGB1, histones (release of nuclear DAMPs following DNA fragmentation), Annexin A1 (ANXA1)

HMGB1, ATP, histones, HSPs

ATP, CRT,

HMGB1, DNA, lipid oxidation products such as 4HNE, LTB4, LTC4, LTD4 and PGE2

ATP, HMGB1

[199,200,201]

Inflammation

Non-inflammatory

Non-inflammatory

Pro-inflammatory

Pro-inflammatory

Pro-inflammatory

Pro-inflammatory

Immunogenicity

Non-immunogenic (may be immunogenic under stress situations like chemotherapy or physical modalities)

Non-immunogenic (may be immunogenic under stress situations like chemotherapy or physical modalities)

Very high

High

High

High

[27]