Disruption of iron homeostasis and resultant health effects upon exposure to various environmental pollutants:A critical review

Environmental pollution has become one of the greatest problems in the world, and the concerns about environmental pollutants released by human activities from agriculture and industrial production have been continuously increasing. Although intense efforts have been made to understand the health effects of environmental pollutants, most studies have only focused on direct toxic effects and failed to simultaneously evaluate the long-term adaptive, compensatory and secondary impacts on health. Burgeoning evidence suggests that environmental pollutants may directly or indirectly give rise to disordered element homeostasis, such as for iron. It is crucially important to maintain concerted cellular and systemic iron metabolism. Otherwise, disordered iron metabolism would lead to cytotoxicity and increased risk for various diseases, including cancers. Thus, study on the effects of environmental pollutants upon iron homeostasis is urgently needed. In this review, we recapitulate the available findings on the direct or indirect impacts of environmental pollutants, including persistent organic pollutants（POPs）, heavy metals and pesticides, on iron homeostasis and associated adverse health problems. In view of the unanswered questions, more efforts are warranted to investigate the disruptive effects of environmental pollutants on iron homeostasis and consequent toxicities.

New insights into disruption of iron homeostasis by environmental pollutants

Among the numerous health conditions environmental pollutants can cause, chronic exposure to pollutants including persistent organic pollutants（POPs） and heavy metals has been shown to disturb a specific biological homeostatic process, the iron metabolism in human body. Disorders of iron metabolism are among the common diseases of humans and encompass a broad spectrum of diseases with different clinical manifestations, ranging from anemia to iron overload, and possibly to neurodegenerative diseases and cancer.Hepcidin–ferroportin（FPN） signaling is one of the key mechanisms responsible for iron supply, utilization, recycling, and storage, and recent studies demonstrated that exposure to environmental pollutants including POPs and heavy metals could lead to disruption of the hepcidin–FPN axis along with disordered systemic iron homeostasis and diseases. This article introduces and highlights the accompanying review article by Drs. Xu and Liu in this journal, which elaborates in detail the adverse effects of environmental pollutants on iron metabolism, and the mechanisms responsible for these toxicological outcomes. It also points out the knowledge gaps still existing in this subject matter. Research that will fill these gaps will improve our understanding of the issue and provide useful information to prevent or treat diseases induced by environmental pollutants.

Iron uptake, signaling, and sensing in plants

Iron (Fe) is an essential micronutrient that affects the growth and development of plants because it participates as a cofactor in numerous physiological and biochemical reactions. As a transition metal, Fe is redoxactive. Fe often exists in soil in the form of insoluble ferric hydroxides that are not bioavailable to plants.Plants have developed sophisticated mechanisms to ensure an adequate supply of Fe in a fluctuating environment. Plants can sense Fe status and modulate the transcription of Fe uptake-associated genes, finallycontrolling Fe uptake from soil to root. There is a critical need to understand the molecular mechanisms bywhich plants maintain Fe homeostasis in response to Fe fluctuations. This review focuses on recentadvances in elucidating the functions of Fe signaling components. Taking Arabidopsis thaliana and Oryzasativa as examples, this review begins by discussing the Fe acquisition systems that control Fe uptake fromsoil, the major components that regulate Fe uptake systems, and the perception of Fe status. Future explorations of Fe signal transduction will pave the way for understanding the regulatory mechanisms that underlie the maintenance of plant Fe homeostasis.