Comparative quantitative proteomics to investigate the remodeling of bioenergetic pathways under iron deficiency inChlamydomonas reinhardtii (original) (raw)

Chemistry and biology of eukaryotic iron metabolism

The International Journal of Biochemistry & Cell Biology, 2001

With rare exceptions, virtually all studied organisms from Archaea to man are dependent on iron for survival. Despite the ubiquitous distribution and abundance of iron in the biosphere, iron-dependent life must contend with the paradoxical hazards of iron deficiency and iron overload, each with its serious or fatal consequences. Homeostatic mechanisms regulating the absorption, transport, storage and mobilization of cellular iron are therefore of critical importance in iron metabolism, and a rich biology and chemistry underlie all of these mechanisms. A coherent understanding of that biology and chemistry is now rapidly emerging. In this review we will emphasize discoveries of the past decade, which have brought a revolution to the understanding of the molecular events in iron metabolism. Of central importance has been the discovery of new proteins carrying out functions previously suspected but not understood or, more interestingly, unsuspected and surprising. Parallel discoveries have delineated regulatory mechanisms controlling the expression of proteins long known -the transferrin receptor and ferritin -as well as proteins new to the scene of iron metabolism and its homeostatic control. These proteins include the iron regulatory proteins , a variety of ferrireductases in yeast an mammalian cells, membrane transporters (DMT1 and ferroportin 1), a multicopper ferroxidase involved in iron export from cells (hephaestin), and regulators of mitochondrial iron balance (frataxin and MFT). Experimental models, making use of organisms from yeast through the zebrafish to rodents have asserted their power in elucidating normal iron metabolism, as well as its genetic disorders and their underlying molecular defects. Iron absorption, previously poorly understood, is now a fruitful subject for research and well on its way to detailed elucidation. The long-sought hemochromatosis gene has been found, and active research is underway to determine how its aberrant functioning results in disease that is easily controlled but lethal when untreated. A surprising connection between iron metabolism and Friedreich's ataxia has been uncovered. It is no exaggeration to say that the new understanding of iron metabolism in health and disease has been explosive, and that what is past is likely to be prologue to what is ahead.

Redox control of iron regulatory proteins

Redox Report, 2002

Iron is an essential cellular constituent but, on the other hand, possesses an enormous toxic capacity when present in excess. This is largely due to Fenton/Haber-Weiss chemistry, e.g. the aerobic iron-catalyzed generation of aggressive radicals, which readily attack and damage cell membranes, proteins and nucleic acids. 1 Thus, the regulation of iron homeostasis poses a challenge not only to satisfy the metabolic needs of cells and organisms for iron, but also to minimize the risk of iron-induced injury.

Regulation of iron uptake minimizes iron-mediated oxidative stress

Journal of Biosciences, 1998

Sequential accommodation of single electrons by the unpaired orbitals of dioxygen yields oxygen radicals (O,~), hydrogen peroxide (H202), hydroxide radicals (OH'), and finally water (H20). Fe 2+ catalyses the formation of the most reactive hydroxide radical fi-om hydrogen peroxide and thus contributes substantially to the toxicity of oxygen. Insolubility of Fe 3. demands the incorporation of iron into transferrin, lactoferrin, ferritin, iron-sulphur clusters, and heine. Bacteria and fungi synthesize low molecular weight compounds, termed siderophores, which are secreted and used to transport Fe 3. into the microbial celIs. Iron is economicalIy used and iron toxicity is minimized by the synthesis of siderophores and ferric siderophore transport systems, and by induction of transport gone transcription by certain Fe3+-loaded siderophores. When cells contain sufficient iron, Fd+-Ioaded Fur protein and Fe'-+-loaded DtxR protein repress gene transcription in Gram-negative bacteria and in most Gram-positive bacteria, respectively. In a recently discovered novel transcription control mechanism, ferric citrate and ferric pseudobactins induce transcription of the iron transport systems by binding to cetl surface receptor proteins without entering the cells. Cytoplasmic sigma factors are activated by a signaling device that involves a protein in the outer membrane and a protein in the cytoplaamic membrane. Both proteins extend into the periplasm to transduce the signal through the space between the two membranes. Intracellular iron homeostasis secured by regulation of iron uptake prevents excessive oxidative stress, which could otherwise overcome the cellular defence and repair systems and kill the cells.

New Perspectives on Iron Uptake in Eukaryotes

Frontiers in Molecular Biosciences

All eukaryotic organisms require iron to function. Malfunctions within iron homeostasis have a range of physiological consequences, and can lead to the development of pathological conditions that can result in an excess of non-transferrin bound iron (NTBI). Despite extensive understanding of iron homeostasis, the links between the "macroscopic" transport of iron across biological barriers (cellular membranes) and the chemistry of redox changes that drive these processes still needs elucidating. This review draws conclusions from the current literature, and describes some of the underlying biophysical and biochemical processes that occur in iron homeostasis. By first taking a broad view of iron uptake within the gut and subsequent delivery to tissues, in addition to describing the transferrin and non-transferrin mediated components of these processes, we provide a base of knowledge from which we further explore NTBI uptake. We provide concise up-to-date information of the transplasma electron transport systems (tPMETSs) involved within NTBI uptake, and highlight how these systems are not only involved within NTBI uptake for detoxification but also may play a role within the reduction of metabolic stress through regeneration of intracellular NAD(P)H/NAD(P) + levels. Furthermore, we illuminate the thermodynamics that governs iron transport, namely the redox potential cascade and electrochemical behavior of key components of the electron transport systems that facilitate the movement of electrons across the plasma membrane to the extracellular compartment. We also take account of kinetic changes that occur to transport iron into the cell, namely membrane dipole change and their consequent effects within membrane structure that act to facilitate transport of ions.

Regulation of cellular iron metabolism

Iron is an essential but potentially hazardous biometal. Mammalian cells require sufficient amounts of iron to satisfy metabolic needs or to accomplish specialized functions. Iron is delivered to tissues by circulating transferrin, a transporter that captures iron released into the plasma mainly from intestinal enterocytes or reticuloendothelial macrophages. The binding of iron-laden transferrin to the cell-surface transferrin receptor 1 results in endocytosis and uptake of the metal cargo. Internalized iron is transported to mitochondria for the synthesis of haem or iron–sulfur clusters, which are integral parts of several metalloproteins, and excess iron is stored and detoxified in cytosolic ferritin. Iron metabolism is controlled at different levels and by diverse mechanisms. The present review summarizes basic concepts of iron transport, use and storage and focuses on the IRE (iron-responsive element)/IRP (iron-regulatory protein) system, a well known post-transcriptional regulatory circuit that not only maintains iron homoeostasis in various cell types, but also contributes to systemic iron balance.

The fate of iron in the organism and its regulatory pathways

Acta medica (Hradec Králové) / Universitas Carolina, Facultas Medica Hradec Králové, 2005

Iron is an essential element involved in many life-necessary processes. Interestingly, in mammals there is no active excretion mechanism for iron. Therefore iron kinetics has to be meticulously regulated. The most important step for regulation of iron kinetics is absorption. The absorption takes place in small intestine and it is implicated that it requires several proteins. Iron is then released from enterocytes into the circulation and delivered to the cells. Iron movement inside the cell is only partially elucidated and its traffic to mitochondia is not known. Surprisingly, the regulation of various proteins related to iron kinetics and energy metabolism at the molecular level is better described. On contrary, the complex control of iron absorption cannot be fully explicated with present knowledge.

A Program for Iron Economy during Deficiency Targets Specific Fe Proteins

Plant physiology, 2018

Iron (Fe) is an essential element for plants, utilized in nearly every cellular process. Because the adjustment of uptake under Fe limitation cannot satisfy all demands, plants need to acclimate their physiology and biochemistry, especially in their chloroplasts, which have a high demand for Fe. To investigate if a program exists for the utilization of Fe under deficiency, we analyzed how hydroponically grown Arabidopsis () adjusts its physiology and Fe protein composition in vegetative photosynthetic tissue during Fe deficiency. Fe deficiency first affected photosynthetic electron transport with concomitant reductions in carbon assimilation and biomass production when effects on respiration were not yet significant. Photosynthetic electron transport function and protein levels of Fe-dependent enzymes were fully recovered upon Fe resupply, indicating that the Fe depletion stress did not cause irreversible secondary damage. At the protein level, ferredoxin, the cytochrome- complex, a...

Regulation of iron metabolism in higher eukaryotes: iron-sulfur centers as genetic switches

The molecular basis for the regulation of cellular iron metabolism in metazoans has been elucidated in the last years. Iron uptake, storage and utilization are coordinately regulated at the post-transcriptional level by mRNA-protein interactions. An increasing number of mRNAs encoding primarily proteins involved in cellular iron turnover, contain iron-responsive elements (IREs), conserved stem-loop structures in their untranslated regions. IREs provide the binding site for two homologous cytoplasmic iron-regulatory proteins, IRPl and IRP2. The iron-regulated IRE/IRP interactions control mRNA translation or stability. Thus, the IRE/IRP system has emerged as a major paradigm of post-transcriptional gene regulation in higher eukaryotes. The studies on IRP1, which appears to be the most abundant iron regulatory protein, have revealed an unexpected role of iron-sulfur clusters as posttranslational regulatory sites and have highlighted the versatility of iron-sulfur chemistry as a determinant of protein function. 132 8 Regulation of iron metabolism in higher eukaryotes acute or chronic iron overload poses a major threat for cells, especially under conditions of 'oxidative stress', where the concentrations of ROS are increased. All living cells, from prokaryotes to multicellular organisms, have adapted to the need for a balanced iron supply by developing elaborate regulatory systems. The regulatory circuit which controls iron homeostasis in higher eukaryotic cells is the main topic of this chapter and will be described below.