Table 2.

Upstream regulatory core substances participate in diabetes complications through the regulation of ferroptosis and ferritinophagy.

Core substances regulated in upstream mechanisms	Possible mechanisms	Induce or inhibit ferroptosis	Diseases	Reference
HIF-1α	Through the enhancement of the HIF-1α/HO-1 pathway, heme decomposition increased, resulting in intracellular iron accumulation	induce	DN	[15]
HMGB1	The NRF2 pathway includes its downstream targets HO-1, NQO-1, GCLC and GCLM	induce	DN	[80]
Sp1	Sp1-mediated upregulation of Prdx6 expression	inhibit	DN	[94]
salusin-β	participate in NRF-2-dependent manner	induce	DN	[95]
TRIM46	upregulate TRIM46, induce ubiquitination and accelerate clearance of GPX4	induce	DR	[102]
HSF1	maintain cellular iron homeostasis and GPX4 expression	inhibit	DCM	[20]
METTL3	METTL3/ASK1-p38 signaling pathway is activated	induce	DO	[123]
NRF2	Regulate iron metabolism homeostasis through NRF2/FPN1 pathway	inhibit	DMIRI	[124]

HIF-1α, hypoxia-inducible factor-1α; HO-1,heme oxygenase-1; HMGB1, high-mobility group box-1; NRF2, nuclear factor E2-related factor2; NQO-1, oxidoreductase1, GCLC, glutathione cysteine ligase catalytic subunit; GCLM, glutathione cysteine ligase modulatory subunit; Sp1, specificity protein 1; Prdx6,peroxiredoxin 6; TRIM46, tripartite motif-containing 46；GPX4，glutathione peroxidase 4; HSF1，heat shock factor 1; METTL3, methyltransferase-like 3; ASK, Apoptosis signal-regulating kinase 1; p38, mitogen-activated protein kinase; FPN1, ferroportin1; DN, diabetic nephropathy; DR, diabetic retinopathy; DCM, diabetic cardiomyopathy; DO, diabetic osteoporosis; DMIRI, diabetic myocardial ischemia-reperfusion injury.