Release of iron from ferritin requires lysosomal activity

Kidane, Theodros Z.; Sauble, Eric; Linder, Maria C.

doi:10.1152/ajpcell.00505.2005

Cited by 237 publications

(209 citation statements)

References 48 publications

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“…Treatment with this Fe(III) chelator for 15 minutes resulted in a significant increase in "free" iron signal (figure 3). Although based on other studies it is known that desferrioxamine treatment for 15 minutes using similar concentrations does not release additional iron into "free" iron pool from iron containing proteins [20,21,33], we carried out fractionation experiments to separate low molecular weight fractions from high molecular weight fractions containing iron. Our study conclusively proved that even up to 2 hour incubation with desferrioxamine does not release iron from high molecular weight iron containing species into low molecular weight iron pool as measured by ICP-MS (data not shown).…”

Section: Discussionmentioning

confidence: 99%

Measuring “free” iron levels in Caenorhabditis elegans using low-temperature Fe(III) electron paramagnetic resonance spectroscopy

Pate

Rangel

Fraser

et al. 2006

Analytical Biochemistry

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Oxidative stress, caused by free radicals within the body, has been associated with the process of aging and many human diseases. As free radicals, in particular superoxide, are difficult to measure, an alternative indirect method for measuring oxidative stress levels has been successfully used in E. coli and yeast. This method is based on a proposed connection between elevated superoxide levels and release of iron from solvent exposed [4Fe-4S] enzyme clusters, which eventually leads to an increase in hydroxyl radical production. In past studies using bacteria and yeast, a positive correlation was found between superoxide production or oxidative stress due to superoxide within the organism and EPR (electron paramagnetic resonance) detectable "free" iron levels. In the present study, we have developed a reliable and an efficient method for measuring "free" iron levels in C. elegans using low temperature Fe(III) EPR at g = 4.3. This method utilizes synchronized worm cultures grown on plates, which are homogenized and treated with desferrioxamine, an Fe(III) chelator, prior to packing the EPR tube. Homogenization was found not to alter "free" iron levels, while desferrioxamine treatment significantly raised these levels, indicating presence of both Fe(II) and Fe(III) in the "free" iron pool. The correlation between free radical levels and the observed "free" iron levels was examined by using heat stress and paraquat treatment. The intensity of the Fe(III) EPR signal and thus, the concentration of the "free" iron pool, varied with the treatments that altered radical levels without changing the total iron levels. This study provides the groundwork needed to uncover the correlation between oxidative stress, "free" iron levels, and longevity in C. elegans.

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Section: Discussionmentioning

confidence: 99%

Measuring “free” iron levels in Caenorhabditis elegans using low-temperature Fe(III) electron paramagnetic resonance spectroscopy

Pate

Rangel

Fraser

et al. 2006

Analytical Biochemistry

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“…The involvement of lysosomes in ferritin degradation and the concomitant iron release has been shown in different cell lines exposed to iron chelating agents (particularly deferoxamine (DFO) or overexpression of FtMt) (Kidane et al 2006;Zhang et al 2010), bacterial infection (Larson et al 2004), and ferroportin activation (Asano et al 2011). Lysosomal inhibitors, but not proteasomal inhibitors, could halt the degradation, induce ferritin accumulation in the organelles and block iron release.…”

Section: Mammalian Ferritin Structurementioning

confidence: 99%

Biology of ferritin in mammals: an update on iron storage, oxidative damage and neurodegeneration

2014

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Iron is an abundant transition metal that is essential for life, being associated to many enzyme and oxygen carrier proteins involved in a variety of fundamental cellular processes. At the same time the metal is potentially toxic due to its capacity to engage in the catalytic production of noxious reactive oxygen species. The control of iron availability in the cells is largely dependent on ferritins, ubiquitous proteins with storage and detoxification capacity. In mammals, cytosolic ferritins are composed of two types of subunits, the H and the L chain, assembled to form a 24-mer spherical cage. Ferritin is present also in mitochondria, in the form of a complex with 24 identical chains. Even though the proteins have been known for a long time, their study is a very active and interesting field yet. In this review we will focus our attention to mammalian cytosolic and mitochondrial ferritins, describing the most recent advancement regarding their storage and antioxidant function, the effects of their genetic mutations in human pathology, and also the possible involvement in non-iron related activities. We will also discuss recent evidence connecting ferritins and the toxicity of iron in a set of neurodegenerative disorder characterized by focal cerebral siderosis. IntroductionThe adaptation of life to an oxic environment required the development of mechanisms to deal with the transformation of the water soluble ferrous ion (Fe 2+ ) to the insoluble ferric ion (Fe 3+ ) and with the concomitant generation of dangerous reactive oxygen species (ROS). The ferritin molecules represent an important and ancient mean developed by organisms in the three domains of life to safely handle the necessary, yet potentially toxic metal. Their ability to detoxify and store the metal through safe oxidation processes protects the cells from undue iron-dependent redox chemistry, while a controlled release of the metal guarantees its availability for different and essential enzymatic reactions. Storage and detoxification of iron represent the main functions of these molecules, and much work has been done to understand the chemical and molecular details of this

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“…When stored iron is needed for synthesis of iron-containing structures, it has to be released from ferritin. Recent research has shown that the major mechanism for this iron release involves lysosomal digestion (Bridges and Hoffman, 1986, Garner et al, 1998, Kidane et al, 2006, Konijn et al, 1999, Kurz et al, 2011, Kwok and Richardson, 2004, Persson et al, 2003, Radisky and Kaplan, 1998, Roberts and Bomford, 1988, Sakaida et al, 1990, Tenopoulou et al, 2005, Vaisman et al, 1997, Yu et al, 2003b, Zhang et al, 2010. Iron is then relocated to the cytoplasm, probably by the participation of DMT1.…”

Section: The Role Of Lysosomes In Intracellular Iron Metabolismmentioning

confidence: 99%

The role of lysosomes in iron metabolism and recycling

Kurz

Eaton

Brunk

2011

The International Journal of Biochemistry & Cell Biology

172

134

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Iron is the most abundant transition metal in the earths crust. It cycles easily between ferric (oxidized; Fe(III)) and ferrous (reduced; Fe(II)) and readily forms complexes with oxygen, making this metal a central player in respiration and related redox processes. However, loose iron, not within heme or iron-sulfur cluster proteins, can be destructively redox-active, causing damage to almost all cellular components, killing both cells and organisms. This may explain why iron is so carefully handled by aerobic organisms. Iron uptake from the environment is carefully limited and carried out by specialized iron transport mechanisms. One reason that iron uptake is tightly controlled is that most organisms and cells cannot efficiently excrete excess iron. When even small amounts of intracellular free iron occur, most of it is safely stored in a non-redox-active form in ferritins. Within nucleated cells, iron is constantly being recycled from aged iron-rich organelles such as mitochondria and used for construction of new organelles. Much of this recycling occurs within the lysosome, an acidic digestive organelle. Because of this, most lysosomes contain relatively large amounts of redox-active iron and are therefore unusually susceptible to oxidant-mediated destabilization or rupture. In many cell types, iron transit through the lysosomal compartment can be remarkably brisk. However, conditions adversely affecting lysosomal iron handling (or oxidant stress) can contribute to a variety of acute and chronic diseases. These considerations make normal and abnormal lysosomal handling of iron central to the understanding and, perhaps, therapy of a wide range of diseases

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Release of iron from ferritin requires lysosomal activity

Abstract: Kidane, Theodros Z., Eric Sauble, and Maria C. Linder. Release of iron from ferritin requires lysosomal activity.

Cited by 237 publications

References 48 publications

Measuring “free” iron levels in Caenorhabditis elegans using low-temperature Fe(III) electron paramagnetic resonance spectroscopy

Measuring “free” iron levels in Caenorhabditis elegans using low-temperature Fe(III) electron paramagnetic resonance spectroscopy

Biology of ferritin in mammals: an update on iron storage, oxidative damage and neurodegeneration

The role of lysosomes in iron metabolism and recycling

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