Synthesis, delivery and regulation of eukaryotic heme and Fe–S cluster cofactors

Barupala, Dulmini; Dzul, Stephen P.; Riggs-Gelasco, Pamela J.; Stemmler, Timothy L.

doi:10.1016/j.abb.2016.01.010

Cited by 32 publications

(27 citation statements)

References 199 publications

(190 reference statements)

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“…Iron (Fe2+) uptake at the surface of cells occurs with the help of DMT1, which encodes a divalent metal transporter that also helps uptake into enterocytes. As a result, the Fe3+-bound transferrin binds the transferrin receptor at the surface of the cell and results in endocytosis [17,30]; Figure 3).…”

Section: Cellular Processing Of Iron and Its Regulationmentioning

confidence: 99%

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Genetic Disorders Associated with Metal Metabolism

Umair

Alfadhel

2019

Cells

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Genetic disorders associated with metal metabolism form a large group of disorders and mostly result from defects in the proteins/enzymes involved in nutrient metabolism and energy production. These defects can affect different metabolic pathways and cause mild to severe disorders related to metal metabolism. Some disorders have moderate to severe clinical consequences. In severe cases, these elements accumulate in different tissues and organs, particularly the brain. As they are toxic and interfere with normal biological functions, the severity of the disorder increases. However, the human body requires a very small amount of these elements, and a deficiency of or increase in these elements can cause different genetic disorders to occur. Some of the metals discussed in the present review are copper, iron, manganese, zinc, and selenium. These elements may play a key role in the pathology and physiology of the nervous system.

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Section: Cellular Processing Of Iron and Its Regulationmentioning

confidence: 99%

“…Within mitochondria, iron is normally stored as mitochondrial ferritin (MTFT). Cytosolic Fe can be converted into FeS proteins and Fe proteins with the help of the PCB1-4-dependent pathway into ferritin [17,30].…”

Section: Cellular Processing Of Iron and Its Regulationmentioning

confidence: 99%

Genetic Disorders Associated with Metal Metabolism

Umair

Alfadhel

2019

Cells

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“…Description of the various porphyrias is out of the scope of the present review; for further information, we recommend to read [38]. Inherited anemias originating from mutations in heme synthesis pathways are further described in section 3.2.…”

Section: Heme Synthesis Pathwaymentioning

confidence: 99%

Rare anemias due to genetic iron metabolism defects

Brissot

Bernard

Brissot

et al. 2018

Mutation Research/Reviews in Mutation Research

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Anemia is defined by a deficiency of hemoglobin, an iron-rich protein that binds oxygen in the blood. It can be due to multiple causes, either acquired or genetic. Alterations of genes involved in iron metabolism may be responsible, usually at a young age, for rare forms of chronic and often severe congenital anemia. These diseases encompass a variety of sideroblastic anemias, characterized by the presence of ring sideroblasts in the bone marrow. Clinical expression of congenital sideroblastic anemia is either monosyndromic (restricted to hematological lineages) or polysyndromic (with systemic expression), depending on whether iron metabolism, and especially heme synthesis, is directly or indirectly affected. Beside sideroblastic anemias, a number of other anemias can develop due to mutations of key proteins acting either on cellular iron transport (such as the DMT1 transporter), plasma iron transport (transferrin), and iron recycling (ceruloplasmin). Contrasting with the aforementioned entities which involve compartmental, and sometimes, systemic iron excess, the iron refractory iron deficiency anemia (IRIDA) corresponds to a usually severe anemia with whole body iron deficiency related to chronic increase of plasma hepcidin, the systemic negative regulator of plasma iron. Once clinically suggested, these diseases are confirmed by genetic testing in specialized laboratories.

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“…Iron metabolism affects the whole cell, since iron is taken up from extracellular space either via transferrin or in a transferrin-independent manner, then reduced in lysosomes for detoxification and distributed within cells, for example to mitochondria, where iron is utilized for ISC production and heme generation [48][49][50]. The correct function of dozens of proteins in mitochondria, cytosol and nucleus depends on the insertion of ISC [51,52], so the regulation of iron homeostasis is crucial. ISC play important roles in a wide range of cellular reactions, e.g.…”

Section: Introductionmentioning

confidence: 99%

Iron Depletion Reduces Abce1 Transcripts While Inducing the Mitophagy Factors Pink1 and Parkin

Key¹,

Sen²,

Arsovic³

et al. 2019

Preprint

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Lifespan extension was recently achieved in Caenorhabditis elegans nematodes by mitochondrial stress and mitophagy, triggered via iron depletion. Conversely in man, deficient mitophagy due to Pink1/Parkin mutations triggers iron accumulation in patient brain and limits survival. We now aimed to identify murine fibroblast factors, which adapt their mRNA expression to acute iron manipulation, relate to mitochondrial dysfunction and may influence survival. After iron depletion, expression of the plasma membrane receptor Tfrc with its activator Ireb2, the mitochondrial membrane transporter Abcb10, the heme-release factor Pgrmc1, the heme-degradation enzyme Hmox1, the heme-binding cholesterol metabolizer Cyp46a1, as well as the mitophagy regulators Pink1 and Parkin showed a negative correlation to iron levels. After iron overload, these factors did not change expression. Conversely, a positive correlation of mRNA levels with both conditions of iron availability was observed for the endosomal factors Slc11a2 and Steap2, as well as for the iron-sulfur-cluster (ISC)-containing factors Ppat, Bdh2 and Nthl1. Positive correlation only after iron depletion was observed for the iron export factor Slc40a1, mitochondrial iron transporters Slc25a28, Abcb7 and Abcb8, mitochondrial ISC-containing factors Glrx5, Nfu1, Bola1 and Abce1, cytosolic Aco1 and Tyw5, as well as nuclear Dna2, Elp3, Pold1 and Prim2. The latter are regulators of nucleotide synthesis and DNA quality control, which have known importance for growth and lifespan. The only Pink1-/- triggered transcript modulation was the reduced expression of the ISC-containing ribosomal factor Abce1. These mammalian findings support previous fly data that Pink1 influences co-translational quality control via Abce1, as well as mitophagy. Our findings provide the first systematic survey how iron dosage triggers homeostatic transcriptional regulations and elucidate how iron deprivation results in mitophagy.

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Synthesis, delivery and regulation of eukaryotic heme and Fe–S cluster cofactors

Cited by 32 publications

References 199 publications

Genetic Disorders Associated with Metal Metabolism

Genetic Disorders Associated with Metal Metabolism

Rare anemias due to genetic iron metabolism defects

Iron Depletion Reduces Abce1 Transcripts While Inducing the Mitophagy Factors Pink1 and Parkin

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