Role and regulation of ferritin H in rotenone-mediated mitochondrial oxidative stress

Mackenzie, Elizabeth L.; Ray, Paul D.; Tsuji, Yoshiaki

doi:10.1016/j.freeradbiomed.2008.01.031

Cited by 47 publications

(28 citation statements)

References 47 publications

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“…Also oxidative stress induced a significant increase (up to 80 fold) in ferritin mRNA (Torti and Torti 2002;Hintze and Theil 2005). A combination of different repressor (Bach1 and ATF1) (Iwasaki et al 2007;Hintze et al 2007) and activators (Nrf2, JunD) (Iwasaki et al 2006;MacKenzie et al 2008) are involved in the recognition and binding of the Antioxidant Response Elements (ARE) in the promoter region of mouse ferritin H and L genes, modulating their expression in response to oxidative stimuli. Different signaling cascades may enroll such DNA binding factors; for instance, the activation of PI3-kinase was required for ferritin H induction by oxidative agents in Jurkat cells (Sakamoto et al 2009); in the same cell type resveratrol, a molecule with antioxidant properties, induced ferritin H transcription via the recruitment of AMP-activated kinase (Iwasaki et al 2013).…”

Section: Regulation Of Ferritin Expressionmentioning

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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Section: Regulation Of Ferritin Expressionmentioning

confidence: 99%

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

2014

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“…We demonstrated that both mouse and human ferritin H genes are transcriptionally activated under oxidative stress via a well-conserved far-upstream enhancer element, antioxidant-responsive element (ARE) (Iwasaki et al, 2006;Tsuji, 2005;Tsuji et al, 1995;Tsuji et al, 2000). The induction of ferritin during oxidative stress is an important cell defence mechanism against oxidative cell damage (Kaur et al, 2003;MacKenzie et al, 2008b;Pham et al, 2004;Sakamoto et al, 2009). …”

Section: Introductionmentioning

confidence: 99%

Transcriptional regulation of ferritin and antioxidant genes by HIPK2 under genotoxic stress

Hailemariam

Iwasaki

Huang

et al. 2010

Journal of Cell Science

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SummaryATF1 (activating transcription factor 1), a stimulus-induced CREB family transcription factor, plays important roles in cell survival and proliferation. Phosphorylation of ATF1 at Ser63 by PKA (cAMP-dependent protein kinase) and related kinases was the only known post-translational regulatory mechanism of ATF1. Here, we found that HIPK2 (homeodomain-interacting protein kinase 2), a DNAdamage-responsive nuclear kinase, is a new ATF1 kinase that phosphorylates Ser198 but not Ser63. ATF1 phosphorylation by HIPK2 activated ATF1 transcription function in the GAL4-reporter system. ATF1 is a transcriptional repressor of ferritin H, the major intracellular iron storage gene, through an ARE (antioxidant-responsive element). HIPK2 overrode the ATF1-mediated ARE repression in a kinase-activity-dependent manner in HepG2 cells. Furthermore, DNA-damage-inducing agents doxorubicin, etoposide and sodium arsenite induced ferritin H mRNA expression in HIPK2 +/+ MEF cells, whereas it was significantly impaired in HIPK2 -/-MEF cells. Induction of other ARE-regulated detoxification genes such as NQO1 (NADPH quinone oxidoreductase 1), GST (glutathione Stransferase) and HO1 (heme oxygenase 1) by genotoxic stress was also decreased in HIPK2-deficient cells. Taken together, these results suggest that HIPK2 is a new ATF1 kinase involved in the regulation of ferritin H and other antioxidant detoxification genes in genotoxic stress conditions.

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“…This argues strongly for the integration of Fe metabolic adaptation as an intrinsic component of inflammation and immunity, presumably contributing to host protection against infection (46,116). FTH transcription is also regulated by the transcription factor NRF2 (112,129), suggesting yet another level of integration between cellular adaptation to oxidative stress and Fe metabolic adaptation during infection. The transcription factor hypoxia-inducible factor alpha and heat shock factor 1 also regulate FTH expression in Caenorhabditis elegans (2), arguing for yet a broader level of integration between Fe metabolic adaptation and cellular responses to different forms of stress associated with inflammation and immunity.…”

Section: Fth and Infectionmentioning

confidence: 99%

Coupling Heme and Iron MetabolismviaFerritin H Chain

Gozzelino

Soares

2014

Antioxidants & Redox Signaling

127

139

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Significance: Inflammation and immunity can be associated with varying degrees of heme release from hemoproteins, eventually leading to cellular and tissue iron (Fe) overload, oxidative stress, and tissue damage. Presumably, these deleterious effects contribute to the pathogenesis of systemic infections. Recent Advances: Heme release from hemoglobin sensitizes parenchyma cells to undergo programmed cell death in response to proinflammatory cytokines, such as tumor necrosis factor. This cytotoxic effect is driven by a mechanism involving intracellular accumulation of free radicals, which sustain the activation of the c-Jun N-terminal kinase ( JNK) signaling transduction pathway. While heme catabolism by heme oxygenase-1 (HO-1) prevents programmed cell death, this cytoprotective effect requires the co-expression of ferritin H (heart/heavy) chain (FTH), which controls the pro-oxidant effect of labile Fe released from the protoporphyrin IX ring of heme. This antioxidant effect of FTH restrains JNK activation, whereas JNK activation inhibits FTH expression, a cross talk that controls metabolic adaptation to cellular Fe overload associated with systemic infections. Critical Issues and Future Directions: Identification and characterization of the mechanisms via which FTH provides metabolic adaptation to tissue Fe overload should provide valuable information to our current understanding of the pathogenesis of systemic infections as well as other immune-mediated inflammatory diseases.

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Role and regulation of ferritin H in rotenone-mediated mitochondrial oxidative stress

Cited by 47 publications

References 47 publications

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

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

Transcriptional regulation of ferritin and antioxidant genes by HIPK2 under genotoxic stress

Coupling Heme and Iron MetabolismviaFerritin H Chain

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