Table 3 Iron and/or copper mediate main causes, related genes and morphological features of cell deaths

Transition metal ions

Fe&

Cu

Fe

Cu

Fe

Cu

Fe

Fe

Cu

Fe

Cu

Cu

Main causes

None reported

ROS or proteasome inhibition

Ferritinophagy

Copper binds to ULK1/ULK2 and GPX4 proteins

ROS accumulation

ROS accumulation

ROS accumulation induces lipid peroxidation

ROS accumulation, Copper binds to GPX4 proteins

Cu binds to DLAT, drives DLAT lipoylation and aggregation

Related genes

Fas↑,Caspase8↑, Caspase4↑, Caspase3↑

BCL-2↓, p-Drp1↓ ,BAX↑, BAD↑,XIAP↑ , Caspase9↑, Caspase3↑

BCL-2↓, Drp1↑, p53↑,BAX↑, XIAP↑ , Caspase9↑, Caspase3↑

NCOA4↑, ATG3↑, ATG5↑, ATG7↑, ATG13↑, MAP1LC3↑

ULK1/ULK2↑, p62↑, ATG3↑, ATG5↑, LC3b /LC3a↑, BECN1↑

p-RIPK1↑, p-RIPK3↑, p-MLKL↑

Tom20↑, Bax↑, caspase3↑, caspase9↑, cleavage GSDME↑, Caspase1↑

Caspase-1↑, IL-1β↑, IL-18↑, NLRP3↑, GRP78↑, GSDMD↑

TFRC↑, STEAP3↑, DMT1↑,SLC7A111↓,SLC3A2↓,GPX4↓,ALOX15↑

ATP7A↓, SLC7A11↓, GPX4↓

SLC31A1↑, ATP7A↓, ATP8A↓, FDX1↑, DLAT↑

Morphological features

Chromatin condenses, nucleus fragmentation, condensation of cytoplasm, forming apoptotic bodies. Then apoptotic bodies are phagocytized by macrophages

The formation of double membrane–layered autophagic vacuoles. Autophagosome fuses to the lysosomes, generating autolysosomes. Autolysosomes are degraded finally

Nuclear and organelle swelling, membrane rupture and DAMPs are released

Nucleus condensation, DNA fragmentation, membrane swelling and rupture, formation of membrane vesicles, and DAMPs are released

Increased mitochondrial membrane density, reduction or disappearance of mitochondrial cristae and cell membrane rupture and blistering

None reported

Reference

[44, 60]

[44, 61,62,63,64,65]

[44, 60, 66,67,68]

[69,70,71]

[68, 72,73,74]

[75, 76]

[77, 78]

[79, 80]

[6]

[72, 81]

[5]