Table 1 Morphological characteristics and key biochemical pathway components of RCD pathways.

From: The multifaceted roles of GSDME-mediated pyroptosis in cancer: therapeutic strategies and persisting obstacles

RCD types

Cellular morphological features

Key biochemical pathway components

Core characteristic (s)

Caspase-dependent

Pore-forming cause

Inflammation features

Immune features

Ref.

Necroptosis

Cytoplasmic swelling, pore formation on cells membranes, loss of plasma membrane integrity, swelling of cytoplasmic organelles, and moderate chromatin condensation.

RIPK1, RIPK3, TRADD, NMEO, caspase-8, and MLKL

Necrosome

MLKL-dependent pores

Inflammatory cell death

Immunogenic cell death

[30, 31]

Apoptosis

Chromatin condensation, plasma membrane blebbing, apoptotic body formation, nuclear fragmentation, cell shrinkage and pyknosis, and phagocytosis by neighboring cells.

Apaf-1, caspase-3/7/8/9, cytochrome c, Bid/tBid, BAX/BAK, BCL-2, and NF-κb

Apoptotic body

No

non-inflammatory

Immunogenic cell death or tolerogenic cell death

[32, 33, 42]

Ferroptosis

Cells swelling, pore formation on cells membranes, smaller mitochondria with decreased cristae, elevated mitochondrial membrane densities, and accumulation of lipid peroxides in plasma membranes

Fe2+, GPX4, ROS, PUFAs, ACSL4, LPCAT3, ALOXs, SLC40A1, TF-TFRC,

Iron accumulation and lipid peroxidation

×

Iron-dependent lipid peroxidation

Inflammatory cell death

Immunogenic cell death

[34, 35]

Cuproptosis

Mitochondrial shrinkage, mitochondrial membrane rupture, reduction in the mitochondrial crest and mitochondrial membrane lysis

Cu+/Cu2+, FDX1, GPX4, SLC31A1, LIAS, ROS, ATP7A/B, GSH

DLAT aggregation and loss of Fe-S cluster

×

No

Undetermined

Immunogenic cell death

[36, 37]

Pyroptosis

Cell swelling, membrane pores formation, membrane rupture, plasma membrane blebbing, moderately condensed chromatin

NLRP3 inflammasome, caspase-1/3/4/5/11, GSDMD, GSDME, IL-1β, and IL-18

Inflammasome

GSDMs-dependent pores

Inflammatory cell death

Immunogenic cell death

[14, 39,40,41]