Searching iron sensors in plants by exploring the link among 2'-OG-dependent dioxygenases, the iron deficiency response and metabolic adjustments occurring under iron deficiency

Abstract

Knowledge accumulated on the regulation of iron (Fe) homeostasis, its intracellular trafficking and transport across various cellular compartments and organs in plants; storage proteins, transporters and transcription factors involved in Fe metabolism have been analyzed in detail in recent years. However, the key sensor(s) of cellular plant "Fe status" triggering the long-distance shoot-root signaling and leading to the root Fe deficiency responses is (are) still unknown. Local Fe sensing is also a major task for roots, for adjusting the internal Fe requirements to external Fe availability: how such sensing is achieved and how it leads to metabolic adjustments in case of nutrient shortage, is mostly unknown. Two proteins belonging to the 2'-OG-dependent dioxygenases family accumulate several folds in Fe-deficient Arabidopsis roots. Such proteins require Fe(II) as enzymatic cofactor; one of their subgroups, the HIF-P4H (hypoxia-inducible factor-prolyl 4-hydroxylase), is an effective oxygen sensor in animal cells. We envisage here the possibility that some members of the 2'-OG dioxygenase family may be involved in the Fe deficiency response and in the metabolic adjustments to Fe deficiency or even in sensing Fe, in plant cells.

Keywords: 2′-OG-dependent dioxygenase; Arabidopsis thaliana; HIF (hypoxia-inducible factor); iron sensor; prolyl 4-hydroxylase.

FIGURE 1

Potential involvement of plant 2′-OG-dioxygenases in Fe sensing, in the Fe deficiency responses and in the metabolic reprogramming occurring under Fe deficiency. Under Fe sufficiency, in presence of the co-factors O₂ and oxoglutarate (OG), 2′-OG-dioxygenases (in green) can catalyze the dioxygenase reaction leading to production of product P from substrate S. Under Fe deficiency, however, at least two scenarios can occur, depending on the K_m of a given 2′-OG-dioxygenase for Fe. If the K_m is close to the physiological concentration of the labile iron pool (LIP; free redox-active Fe ions), upon reduction of Fe availability, the enzymatic activity of the 2′-OG-dioxygenase is drastically reduced or fully inhibited and the reduction or complete lack of enzymatic product can be itself a signal of “Fe deficiency” triggering the Fe deficiency response cascades (upper panel, right). If instead K_m is far below the physiological LIP, the enzyme might still be active (lower panel, right). Not only, if transcriptional/translational up-regulation of such 2′-OG-dioxygenase takes place under Fe deficiency, then an increased total enzymatic activity can lead to higher production of product P (lower panel, right). Product P, in turn, could be involved in the Fe response/metabolic adjustments occurring under Fe deficiency.