RESUMO
Frataxin plays a key role in eukaryotic cellular iron metabolism, particularly in mitochondrial heme and iron-sulfur (Fe-S) cluster biosynthesis. However, its precise role has yet to be elucidated. In this work, we studied the subcellular localization of Arabidopsis frataxin, AtFH, using confocal microscopy, and found a novel dual localization for this protein. We demonstrate that plant frataxin is targeted to both the mitochondria and the chloroplast, where it may play a role in Fe-S cluster metabolism as suggested by functional studies on nitrite reductase (NIR) and ferredoxin (Fd), two Fe-S containing chloroplast proteins, in AtFH deficient plants. Our results indicate that frataxin deficiency alters the normal functioning of chloroplasts by affecting the levels of Fe, chlorophyll, and the photosynthetic electron transport chain in this organelle.
Assuntos
Proteínas de Arabidopsis/fisiologia , Arabidopsis/metabolismo , Cloroplastos/metabolismo , Proteínas de Ligação ao Ferro/fisiologia , Proteínas Ferro-Enxofre/metabolismo , Mitocôndrias/metabolismo , Arabidopsis/genética , Arabidopsis/ultraestrutura , Proteínas de Arabidopsis/análise , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Clorofila/análise , Cloroplastos/química , Ferredoxinas/genética , Ferredoxinas/metabolismo , Deleção de Genes , Proteínas de Ligação ao Ferro/análise , Proteínas de Ligação ao Ferro/genética , Microscopia Confocal , Mitocôndrias/química , Proteínas Mitocondriais/fisiologia , Nitrito Redutases/genética , Nitrito Redutases/metabolismo , Plantas Geneticamente Modificadas , Protoplastos/metabolismo , Protoplastos/ultraestrutura , RNA Mensageiro/genética , RNA de Plantas/genética , Reação em Cadeia da Polimerase em Tempo RealRESUMO
Autosomal recessive cerebellar ataxias belong to a broader group of disorders known as inherited ataxias. In most cases onset occurs before the age of 20. These neurological disorders are characterized by degeneration or abnormal development of the cerebellum and spinal cord. Currently, specific treatment is only available for some of the chronic ataxias, more specifically those related to a known metabolic defect, such as abetalipoproteinemia, ataxia with vitamin E deficiency, and cerebrotendinous xanthomatosis. Treatment based on a diet with reduced intake of fat, supplementation of oral vitamins E and A, and the administration of chenodeoxycholic acid could modify the course of the disease. Although for most of autosomal recessive ataxias there is no definitive treatment, iron chelators and antioxidants have been proposed to reduce the mitochondrial iron overload in Friederich's ataxia patients. Corticosteroids have been used to reduce ataxia symptoms in ataxia telangiectasia. Coenzyme Q10 deficiency associated with ataxia may be responsive to Co Q10 or ubidecarenone supplementations. Early treatment of these disorders may be associated with a better drug response.
Assuntos
Ataxia Cerebelar/tratamento farmacológico , Corticosteroides/uso terapêutico , Ataxia/tratamento farmacológico , Ataxia Cerebelar/etiologia , Doença Crônica , Ataxia de Friedreich/tratamento farmacológico , Humanos , Proteínas de Ligação ao Ferro/fisiologia , Doenças Mitocondriais/tratamento farmacológico , Debilidade Muscular/tratamento farmacológico , Ubiquinona/deficiência , Vitamina E/uso terapêutico , Deficiência de Vitamina E/complicações , FrataxinaRESUMO
Autosomal recessive cerebellar ataxias belong to a broader group of disorders known as inherited ataxias. In most cases onset occurs before the age of 20. These neurological disorders are characterized by degeneration or abnormal development of the cerebellum and spinal cord. Currently, specific treatment is only available for some of the chronic ataxias, more specifically those related to a known metabolic defect, such as abetalipoproteinemia, ataxia with vitamin E deficiency, and cerebrotendinous xanthomatosis. Treatment based on a diet with reduced intake of fat, supplementation of oral vitamins E and A, and the administration of chenodeoxycholic acid could modify the course of the disease. Although for most of autosomal recessive ataxias there is no definitive treatment, iron chelators and antioxidants have been proposed to reduce the mitochondrial iron overload in Friederichs ataxia patients. Corticosteroids have been used to reduce ataxia symptoms in ataxia telangiectasia. Coenzyme Q10 deficiency associated with ataxia may be responsive to Co Q10 or ubidecarenone supplementations. Early treatment of these disorders may be associated with a better drug response.
Assuntos
Ataxia Cerebelar/tratamento farmacológico , Ataxia Cerebelar/etiologia , Ataxia de Friedreich/tratamento farmacológico , Ataxia/tratamento farmacológico , Corticosteroides/uso terapêutico , Debilidade Muscular/tratamento farmacológico , Deficiência de Vitamina E/complicações , Doença Crônica , Doenças Mitocondriais/tratamento farmacológico , Humanos , Proteínas de Ligação ao Ferro/fisiologia , Ubiquinona/deficiência , Vitamina E/uso terapêuticoRESUMO
Autosomal recessive cerebellar ataxias belong to a broader group of disorders known as inherited ataxias. In most cases onset occurs before the age of 20. These neurological disorders are characterized by degeneration or abnormal development of the cerebellum and spinal cord. Currently, specific treatment is only available for some of the chronic ataxias, more specifically those related to a known metabolic defect, such as abetalipoproteinemia, ataxia with vitamin E deficiency, and cerebrotendinous xanthomatosis. Treatment based on a diet with reduced intake of fat, supplementation of oral vitamins E and A, and the administration of chenodeoxycholic acid could modify the course of the disease. Although for most of autosomal recessive ataxias there is no definitive treatment, iron chelators and antioxidants have been proposed to reduce the mitochondrial iron overload in Friederichs ataxia patients. Corticosteroids have been used to reduce ataxia symptoms in ataxia telangiectasia. Coenzyme Q10 deficiency associated with ataxia may be responsive to Co Q10 or ubidecarenone supplementations. Early treatment of these disorders may be associated with a better drug response.
Assuntos
Ataxia Cerebelar/tratamento farmacológico , Corticosteroides/uso terapêutico , Ataxia/tratamento farmacológico , Ataxia Cerebelar/etiologia , Doença Crônica , Ataxia de Friedreich/tratamento farmacológico , Humanos , Proteínas de Ligação ao Ferro/fisiologia , Doenças Mitocondriais/tratamento farmacológico , Debilidade Muscular/tratamento farmacológico , Ubiquinona/deficiência , Vitamina E/uso terapêutico , Deficiência de Vitamina E/complicaçõesRESUMO
Frataxin is a nuclear-encoded mitochondrial protein highly conserved in prokaryotes and eukaryotes. Its deficiency was initially described as the phenotype of Friedreich's ataxia, an autosomal recessive disease in humans. Although several functions have been described for frataxin, that is, involvement in Fe-S cluster and heme synthesis, energy conversion and oxidative phosphorylation, iron handling and response to oxidative damage, its precise function remains unclear. Although there is a general consensus on the participation of frataxin in the maintenance of cellular iron homeostasis and in iron metabolism, this protein may have other specific functions in different tissues and organisms.
Assuntos
Proteínas de Ligação ao Ferro/fisiologia , Sequência de Aminoácidos , Animais , Heme/metabolismo , Humanos , Ferro/metabolismo , Proteínas de Ligação ao Ferro/química , Proteínas de Ligação ao Ferro/metabolismo , Proteínas Ferro-Enxofre/metabolismo , Mitocôndrias/metabolismo , Dados de Sequência Molecular , Ligação Proteica , Estrutura Terciária de Proteína , Homologia de Sequência de Aminoácidos , Transdução de Sinais , FrataxinaRESUMO
Iron is a key element in plant nutrition. Iron deficiency as well as iron overload results in serious metabolic disorders that affect photosynthesis, respiration and general plant fitness with direct consequences on crop production. More than 25% of the cultivable land possesses low iron availability due to high pH (calcareous soils). Plant biologists are challenged by this concern and aimed to find new avenues to ameliorate plant responses and keep iron homeostasis under control even at wide range of iron availability in various soils. For this purpose, detailed knowledge of iron uptake, transport, storage and interactions with cellular compounds will help to construct a more complete picture of its role as essential nutrient. In this review, we summarize and describe the recent findings involving four central players involved in keeping cellular iron homeostasis in plants: nitric oxide, ferritin, frataxin and nitrosyl iron complexes. We attempt to highlight the interactions among these actors in different scenarios occurring under iron deficiency or iron overload, and discuss their counteracting and/or coordinating actions leading to the control of iron homeostasis.