FPN regulation Mechanism . Mediator .... | American Society of Hematology

FPN regulation

Mechanism	Mediator	Expression	Effector	Target	Major cell types	Main role
Transcription	Oxidative stress	Up	NRF2	ARE	Macrophage	Erythrophagocytosis
	Heme	Up	BACH1 inactivation	ARE	Macrophage	Erythrophagocytosis
	Hypoxia	Up	HIF2α	HRE	Enterocyte	Dietary iron absorption
	Endotoxin	Down	TLR signaling	?	Macrophage	Inflammation
Post-transcription*	Decreased cellular iron	Down	miR-485-3p	3' UT	Multiple	Intracellular iron homeostasis
Translation	Decreased cellular iron	Down	IRP	5' UT IRE (FPN1A)†	Low iron flux	Intracellular iron homeostasis
Cell surface degradation	Hepcidin	Down	Ubiquitination	EC Loop C326	High iron flux	Systemic iron homeostasis Inflammation Erythropoiesis
Functional activity	Hepcidin	Unchanged	Steric hindrance	Iron efflux	High iron flux	Systemic iron homeostasis Inflammation Erythropoiesis

Mechanism	Mediator	Expression	Effector	Target	Major cell types	Main role
Transcription	Oxidative stress	Up	NRF2	ARE	Macrophage	Erythrophagocytosis
	Heme	Up	BACH1 inactivation	ARE	Macrophage	Erythrophagocytosis
	Hypoxia	Up	HIF2α	HRE	Enterocyte	Dietary iron absorption
	Endotoxin	Down	TLR signaling	?	Macrophage	Inflammation
Post-transcription*	Decreased cellular iron	Down	miR-485-3p	3' UT	Multiple	Intracellular iron homeostasis
Translation	Decreased cellular iron	Down	IRP	5' UT IRE (FPN1A)†	Low iron flux	Intracellular iron homeostasis
Cell surface degradation	Hepcidin	Down	Ubiquitination	EC Loop C326	High iron flux	Systemic iron homeostasis Inflammation Erythropoiesis
Functional activity	Hepcidin	Unchanged	Steric hindrance	Iron efflux	High iron flux	Systemic iron homeostasis Inflammation Erythropoiesis

Not further characterized.

†

Not in enterocytes, erythroid cells.

ARE, antioxidant response element; EC, extracellular; HRE, hypoxia response element, IRE, iron response element; IRP, iron regulatory protein; miR, microRNA; UT, untranslated.

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