Table 3.

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

Iron and/or copper mediated cell death	Extrinsic apoptosis	Intrinsic apoptosis			Autophagy dependent cell death		Necroptosis	Pyroptosis			Ferroptosis		Cuproptosis
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, 61–65]		[44, 60, 66–68]	[69–71]	[68, 72–74]	[75, 76]	[77, 78]		[79, 80]	[6]	[72, 81]	[5]